The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
Open accessAbstract
Apoptosis in vivo is followed almost inevitably by rapid uptake into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, or resolution of inflammation. Phagocytosis of apoptotic cells by macrophages has been suggested to be a quiet process that does not lead to production of inflammatory mediators. Here we show that phagocytosis of apoptotic neutrophils (in contrast to immunoglobulin G-opsonized apoptotic cells) actively inhibited the production of interleukin (IL)-1beta, IL-8, IL-10, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha, as well as leukotriene C4 and thromboxane B2, by human monocyte-derived macrophages. In contrast, production of transforming growth factor (TGF)-beta1, prostaglandin E2, and platelet-activating factor (PAF) was increased. The latter appeared to be involved in the inhibition of proinflammatory cytokine production because addition of exogenous TGF-beta1, prostaglandin E2, or PAF resulted in inhibition of lipopolysaccharide-stimulated cytokine production. Furthermore, anti-TGF-beta antibody, indomethacin, or PAF receptor antagonists restored cytokine production in lipopolysaccharide-stimulated macrophages that had phagocytosed apoptotic cells. These results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages. Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production. Disorders in either could result in chronic inflammatory diseases.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Some of the more common cytokines used in biomaterial‐based research involves the proinflammatory IFN‐γ or IL‐4, which are important effectors in steering the macrophage phenotypes.[ 103 , 232 , 233 , 234 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [234]
In the citing paper
“Interestingly, phagocytosis of neutrophils is also a central element to induce the phenotype switch of macrophages from pro-inflammatory M1 to a reparative M2 phenotype [73].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [73]
In the citing paper
“2-AG increases the number of phagocytosing macrophages, which leads to increased production of anti-inflammatory cytokines, e.g., TGF-β1 and decreased output of pro-inflammatory cytokines, e.g., TNF-α by macrophages [73].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [73]
In the citing paper
“Their apoptosis and engulfment by macrophages (efferocytosis) provides a key signal to the local immune milieu, including macrophages, to transition to an anti-inflammatory, pro-repair state”
From Immunology of Wound Healing (2018) · cites this paper as [47]
In the citing paper
“In physiologic wound repair, neutrophils undergo apoptosis after carrying out their various functions at the site of injury. Local macrophage uptake of apoptotic neutrophils then triggers a transition out of inflammatory phase [47–49].”
From Immunology of Wound Healing (2018) · cites this paper as [47]
In the citing paper
“Macrophages in the wound site are responsible for phagocytosis of apoptotic neutrophils, a process known as efferocytosis [73••]. This action itself induces macrophages to transition from a pro-inflammatory phenotype, to an anti-inflammatory phenotype”
From Immunology of Wound Healing (2018) · cites this paper as [47]
Citations
Cites
Cell Death: The Significance of Apoptosis
Wyllie, A. H., Kerr, J. F. R., & Currie, A. R. (1980) · International review of cytology · doi:10.1016/s0074-7696(08)62312-8 · Cited by 7,151
Cytokine-mediated regulation of CXCR4 expression in human neutrophils
Nagase, H., Miyamasu, M., Yamaguchi, M., Imanishi, M., Tsuno, N. H., Matsushima, K., Yamamoto, K., Morita, Y., & Hirai, K. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.4.711 · Cited by 4,713
de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C. G., & de Vries, J. E. (1991) · The Journal of experimental medicine · doi:10.1084/jem.174.5.1209 · Cited by 3,762
Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J., Bratton, D. L., & Henson, P. M. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.7.2207 · Cited by 3,321
Self-citationShull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985
IL-10 inhibits cytokine production by activated macrophages
Fiorentino, D. F., Zlotnik, A., Mosmann, T. R., Howard, M., & O’Garra, A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.11.3815 · Cited by 2,888
Martin, S. J., Reutelingsperger, C. P., McGahon, A. J., Rader, J. A., van Schie, R. C., LaFace, D. M., & Green, D. R. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.5.1545 · Cited by 2,824
Koopman, G., Reutelingsperger, C. P. M., Kuijten, G., Keehnen, R. M. J., Pals, S. T., & van Oers, M. H. J. (1994) · Blood · doi:10.1182/blood.v84.5.1415.1415 · Cited by 2,687
Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.770 · Cited by 1,967
Savill, J. S., Wyllie, A. H., Henson, J. E., Walport, M. J., Henson, P. M., & Haslett, C. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113970 · Cited by 1,536
Self-citation
Cited by
Sorted by citations
Items 601–700 of 1,020
Efferocytosis and Its Role in Inflammatory Disorders
Ge, Y., Huang, M., & Yao, Y.-M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.839248 · Cited by 150
“The scavenger receptors SR-A1, SR-B1, and CD36 recognize PS and promote efferocytosis by macrophages (Fadok et al., 1998b; Terpstra and van Berkel, 2000).”
BackgroundApoptosis: the quiet death silences the immune system
Sun, E., & Shi, Y. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00164-4 · Cited by 138
“In the meantime, Fadok et al. (1998) reported that macrophages ingesting apoptotic neutrophils decreased pro-inflammatory cytokines and increased immunosuppressive cytokines, such as transforming growth factor (TGF)-b1, prostaglandin E2, and platelet-activating factor.”
BackgroundPhosphatidylserine on HIV Envelope Is a Cofactor for Infection of Monocytic Cells
Callahan, M. K., Popernack, P. M., Tsutsui, S., Truong, L., Schlegel, R., & Henderson, A. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.9.4840 · Cited by 138
“Although we have not seen any effects on HIV-1 transcription in infected monocytes/macrophages treated with annexin V or PS vesicles, we cannot rule out that PS recognized in the context of a virus particle or apoptotic cell alters HIV-1 expression (54, 55).”
BackgroundNeutrophil Development, Migration, and Function in Teleost Fish
Havixbeck, J. J., & Barreda, D. R. (2015) · Biology · doi:10.3390/biology4040715 · Cited by 147
Hart, S. P., Ross, J. A., Ross, K., Haslett, C., & Dransfield, I. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400680 · Cited by 137
“Furthermore, apoptosis is associated with cell surface changes that provide signals for the recognition and phagocytosis of dying granulocytes by macrophages,(7) a process that results in inhibition of macrophage cytokine production in vitro.(8) By down-regulating potentially harmful neutrophil functions and triggerin…”
Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells
Hirt, U. A., & Leist, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401286 · Cited by 138
“10 In contrast to the phagocytosis of microbes, the uptake of apoptotic cells commits macrophages to release anti-inflammatory factors, such as TGFb, 11,12 and to inhibit the secretion of proinflammatory mediators such as TNFa.”
BackgroundInfluentialBittencourt, M. D. C., Perruche, S., Contassot, E., Fresnay, S., Baron, M.-H., Angonin, R., Aubin, F., Hervé, P., Tiberghien, P., & Saas, P. (2001) · Blood · doi:10.1182/blood.v98.1.224 · Cited by 137
Bacteria and Antibiotics in Wound Healing
Caldwell, M. D. (2020) · Surgical Clinics of North America · doi:10.1016/j.suc.2020.05.007 · Cited by 136
Shared signaling systems in myeloid cell-mediated muscle regeneration
Tidball, J. G., Dorshkind, K. A., & Wehling‐Henricks, M. (2014) · Development · doi:10.1242/dev.098285 · Cited by 151
“…phenotype with changes in cytokine exposure, at least in vitro, the phagocytosis of cellular debris is sufficient to switch macrophages from an M1 to an M2 phenotype without changes in the activation by cytokines (Fadok et al., 1998; Fadok et al., 2001; Arnold et al., 2007; Mounier et al., 2013).”
BackgroundPersistence of apoptotic cells without autoimmune disease or inflammation in CD14−/− mice
Devitt, A., Parker, K., Ogden, C. A., Oldreive, C., Clay, M., Melville, L. A., Bellamy, C. O. C., Lacy‐Hulbert, A., Gangloff, S. C., Goyert, S. M., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200410057 · Cited by 137
“In vitro studies have shown that CD14 also plays a significant role in the clearance of apoptotic cells by both human and murine macrophages (Flora and Gregory, 1994; Devitt et al., 1998; Fadok et al., 1998b; Schlegel et al., 1999).”
BackgroundResultInfluentialLymphocytes are detrimental during the early innate immune response against Listeria monocytogenes
Carrero, J. A., Calderón, B., & Unanue, E. R. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060045 · Cited by 135
Mitochondrial mechanisms of sepsis-induced organ failure.
Exline, M. C., & Crouser, E. D. (2008) · PubMed · doi:10.2741/3061 · Cited by 134
Fischer‐Posovszky, P., Wang, Q. A., Asterholm, I. W., Rutkowski, J. M., & Scherer, P. E. (2011) · Endocrinology · doi:10.1210/en.2011-1031 · Cited by 138
Nepal, S., Tiruppathì, C., Tsukasaki, Y., Farahany, J., Mittal, M., Rehman, J., Prockop, D. J., & Malik, A. B. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821601116 · Cited by 136
The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of the acute MS lesion
Barnett, M. H., Henderson, A. P. D., & Prineas, J. W. (2006) · Multiple Sclerosis Journal · doi:10.1191/135248506ms1304rr · Cited by 134
“Such interaction also results in the suppression of inflammatory mediator production and inhibition of immune responses, possibly mediated by TGF-b, prostaglandin E and IL-10 [44].”
BackgroundMold, C., Baca, R., & Clos, T. W. D. (2002) · Journal of Autoimmunity · doi:10.1006/jaut.2002.0615 · Cited by 134
Duran, G. A., Krysko, D. V., Kaczmarek, A., Petrovski, G., Vandenabeele, P., & Fésüs, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040069 · Cited by 137
“The anti-inflammatory features of apoptotic cells resulting from surface exposure of anti-inflammatory molecules such as phosphatidylserine have been known for some time [7,8].”
BackgroundHallett, J. M., Leitch, A. E., Riley, N. A., Duffin, R., Haslett, C., & Rossi, A. G. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.03.002 · Cited by 134
Requirements for Apoptotic Cell Contact in Regulation of Macrophage Responses
Lucas, M., Stuart, L. M., Zhang, A., Hodivala‐Dilke, K., Febbraio, M., Silverstein, R. L., Savill, J., & Lacy‐Hulbert, A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.4047 · Cited by 133
Nanomedicine Delivers Promising Treatments for Rheumatoid Arthritis
Prasad, L. K., O’Mary, H. L., & Cui, Z. (2015) · Nanomedicine · doi:10.2217/nnm.15.45 · Cited by 132
Nazmi, A., Field, R. H., Griffin, É. W., Haugh, O., Hennessy, E., Cox, D. J., dos Reis, R. R., Tortorelli, L. S., Murray, C., López-Rodríguez, A. B., et al. (2019) · Glia · doi:10.1002/glia.23592 · Cited by 133
“PGE2 is secreted by macrophages and microglia undertaking phagocytosis of apoptotic cells (De Simone, Ajmone-Cat, Tirassa, & Minghetti, 2003; Fadok et al., 1998) in a TGFβ1-dependent manner (Freire-de-Lima et al.”
BackgroundGentile, P., & Garcovich, S. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060855 · Cited by 133
Morimoto, K., Amano, H., Sonoda, F., Baba, M., Senba, M., Yoshimine, H., Yamamoto, H., Ii, T., Oishi, K., & Nagatake, T. (2001) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.24.5.4292 · Cited by 132
Cytokine fields and the polarization of the immune response
Kourilsky, P. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)02012-9 · Cited by 132
Silverstein, R. L., & Febbraio, M. (2000) · Current Opinion in Lipidology · doi:10.1097/00041433-200010000-00006 · Cited by 132
Ribeiro-Gomes, F. L., Moniz‐de‐Souza, M. C. A., Alexandre‐Moreira, M. S., Dias, W. B., Lopes, M. F., Nunes, M. P., Lungarella, G., & DosReis, G. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.3988 · Cited by 134
Cunin, P., Beauvillain, C., Miot, C., Augusto, J., Preisser, L., Blanchard, S., Pignon, P., Scotet, M., Garo, E., Frémaux, I., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.113 · Cited by 132
“immunoregulatory cytokines (TGFβ, IL-10) and low or no proinflammatory cytokines and chemokines.(51) In this immunoregulatory environment, the presentation and crosspresentation of apoptotic cell antigens by APCs maintain peripheral T-cell tolerance.”
BackgroundWhitlock, B. B., Gardai, S. J., Fadok, V. A., Bratton, D. L., & Henson, P. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.6.1305 · Cited by 131
“In this latter situation, engulfment of apoptotic neutrophils by phagocytes both eliminates potentially damaging proinflammatory substances and stimulates the production of antiinflammatory mediators (Fadok et al., 1998).”
BackgroundSelf-citationNami, Y., Abdullah, N., Haghshenas, B., Radiah, D., Rosli, R., & Khosroushahi, A. (2014) · Microbiology and immunology · doi:10.1111/1348-0421.12175 · Cited by 129
“This type of cell death is frequently associated with phagocytosis by resident tissue macrophages and the release of antiinflammatory cytokines (62).”
BackgroundGriffiths, M., Gasque, P., & Neal, J. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181996688 · Cited by 130
“The identity of the receptors and ligands responsible for engulfment is not clear, but PS binds to C1q and the calreticulin (C1qR)/CD91 complex (60, 72, 79, 80).”
BackgroundInfluentialHamada, T., Torikai, M., Kuwazuru, A., Tanaka, M., Horai, N., Fukuda, T., Yamada, S., Nagayama, S., Hashiguchi, K., Sunahara, N., et al. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23729 · Cited by 130
Subversion of Host Recognition and Defense Systems by Francisella spp
Jones, C. L., Napier, B. A., Sampson, T. R., Llewellyn, A. C., Schroeder, M. R., & Weiss, D. S. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05027-11 · Cited by 135
Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation
Marwick, J. A., Mills, R., Kay, O., Michail, K., Stephen, J., Rossi, A. G., Dransfield, I., & Hirani, N. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0710-y · Cited by 136
Zheng, L., He, M. Y., Long, M., Blomgran, R., & Stendahl, O. I. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.6319 · Cited by 129
Chronic exposure to TGFβ1 regulates myeloid cell inflammatory response in an IRF7-dependent manner
Cohen, M., Matcovitch, O., David, E., Barnett‐Itzhaki, Z., Keren‐Shaul, H., Blecher‐Gonen, R., Jaitin, D. A., Sica, A., Amit, I., & Schwartz, M. (2014) · The EMBO Journal · doi:10.15252/embj.201489293 · Cited by 142
“Moreover, TGF b 1 is involved in mitigating inflammation, promoting resolution (Fadok et al , 1998; Wyss-Coray et al , 2001; Huynh et al , 2002; McGeachy et al , 2007), and is highly expressed relative to the other isoforms in the spinal cord following spinal cord injury (SCI) (Shechter et al ,…”
Transcriptional and Translational Regulation of TGF-β Production in Response to Apoptotic Cells
Xiao, Y. Q., Freire-de-Lima, C. G., Schiemann, W. P., Bratton, D. L., Vandivier, R. W., & Henson, P. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.5.3575 · Cited by 131
“Thus, in our previous studies, we have demonstrated that interaction of phagocytes with apoptotic cells through PS results in production of the active TGF- both in vitro and in vivo (6, 8, 9).”
BackgroundSelf-citationA Close Encounter of the Third Kind
Mildner, A., Yona, S., & Jung, S. (2013) · Advances in immunology · doi:10.1016/b978-0-12-417028-5.00003-x · Cited by 136
Immune Response Against Dying Tumor Cells
Zitvogel, L., Casares, N., Péquignot, M. O., Chaput, N., Albert, M. L., & Kroemer, G. (2004) · Advances in immunology · doi:10.1016/s0065-2776(04)84004-5 · Cited by 137
Sjögren’s Syndrome-Like Ocular Surface Disease in Thrombospondin-1 Deficient Mice
Turpie, B., Yoshimura, T., Gulati, A., Ríos, J. D., Dartt, D. A., & Masli, S. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081058 · Cited by 129
Immunosenescence and Challenges of Vaccination against Influenza in the Aging Population.
Reber, A. J., Chirkova, T., Kim, J. H., Cao, W., Biber, R., Shay, D. K., & Sambhara, S. R. (2012) · Europe PMC (PubMed Central) · Cited by 133
Cellular and nuclear degradation during apoptosis
He, B., Lü, N., & Zhou, Z. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.008 · Cited by 131
“Macrophages that engulf apoptotic cells even elicit anti-inflammatory responses that facilitate the resolution of regional inflammation [9-12].”
BackgroundD’Ávila, H., Freire-de-Lima, C. G., Roque, N. R., Teixeira, L., Barja‐Fidalgo, C., Silva, A. R., Melo, R. C. N., DosReis, G. A., Castro-Faria-Neto, H. C., & Bozza, P. T. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir432 · Cited by 132
HMGB1 inhibits macrophage activity in efferocytosis through binding to the αvβ3-integrin
Friggeri, A., Yang, Y., Banerjee, S., Park, Y.-J., Liu, G., & Abraham, E. H. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00152.2010 · Cited by 132
Denny, M. F., Chandaroy, P., Killen, P. D., Caricchio, R., Lewis, E. E., Richardson, B. C., Lee, K.-D., Gavalchin, J., & Kaplan, M. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2095 · Cited by 128
Yagnik, D. R., Evans, B., Florey, O., Mason, J. C., Landis, R. C., & Haskard, D. O. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20317 · Cited by 128
“One mechanism by which TGF 1 could be generated during MSU crystal–induced inflammation is through the stimulation of macrophages by apoptotic neutrophils (14).”
BackgroundChemokines in host–parasiteinteractions in leishmaniasis
Teixeira, M. J., Teixeira, C., Andrade, B. B., et al. (2005) · Trends in Parasitology · doi:10.1016/j.pt.2005.11.010 · Cited by 128
Green, D. R., & Beere, H. M. (2000) · Nature · doi:10.1038/35011175 · Cited by 128
Macrophages and Cardiovascular Health
Frodermann, V., & Nahrendorf, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00068.2017 · Cited by 128
“Like IL-10 and TGF- , neutralizing IL-4 could thus be of potential therapeutic interest in heart failure.”
BackgroundInfluentialMonaghan, M. G., Borah, R., Thomsen, C., & Browne, S. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115120 · Cited by 131
Hart, S. P., Smith, J. R., & Dransfield, I. (2004) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2003.02330.x · Cited by 130
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways
A-González, N., & Castrillo, A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.015 · Cited by 139
“M1 classic activation and the release of anti-inflammatory molecules such as IL-10 and TGFβ [102,103].”
BackgroundInfluentialSchmidt, F. I., Bleck, C. K. E., & Mercer, J. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.11.007 · Cited by 125
“Uptake of apoptotic bodies elicits anti-inflammatory signals [35] and it is intriguing to speculate that VACV infection could benefit from such modifications of the host immune system.”
BackgroundScull, C. M., Hays, W. D., & Fischer, T. (2010) · Journal of Inflammation · doi:10.1186/1476-9255-7-53 · Cited by 128
“A major function of macrophages is phagocytosis of cellular and acellular debris during inflammation and wound healing, and the activation response of macrophages following phagocytosis can be varied depending on the local extracellular environment [1-6].”
BackgroundResultTLR-2 and TLR-9 are sensors of apoptosis in a mouse model of doxorubicin-induced acute inflammation
Krysko, D. V., Kaczmarek, A., Krysko, O., Heyndrickx, L., Woznicki, J., Bogaert, P., Cauwels, A., Takahashi, N., Magez, S., Bachert, C., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.4 · Cited by 129
Mer receptor tyrosine kinase mediates both tethering and phagocytosis of apoptotic cells
Dransfield, I., Zagórska, A., Lew, E. D., Michail, K., & Lemke, G. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.18 · Cited by 125
“Apoptotic cell (AC) clearance normally eliminates a plethora of pro-inflammatory stimuli,(8,9) and the recognition of ACs by phagocytes(10) limits progression to necrosis,(11) suppresses pro-inflammatory mediator production, and induces IL-10 and TGF-β release.(12,13) As defective clearance of ACs is associated with t…”
BackgroundThe Role of Efferocytosis in Autoimmune Diseases
Abdolmaleki, F., Farahani, N., Hayat, S. M. G., Pirro, M., Bianconi, V., Barreto, G. E., & Sahebkar, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01645 · Cited by 129
“In order to maintain tissue homeostasis and to prevent inflammation, phagocytes with engulfed dead cells can produce anti-inflammatory cytokines, including TGFβ and interleukin-10 (80).”
BackgroundKuhn, A., Wenzel, J., & Weyd, H. (2014) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-013-8403-x · Cited by 127
Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica
Nakada‐Tsukui, K., & Nozaki, T. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00175 · Cited by 127
“This observation is consistent with the theory that clearance of dead cells and debris by phagocytosis helps to minimize pro-inflammatory responses (145, 146).”
ResultMacrophage Surface Expression of Annexins I and II in the Phagocytosis of Apoptotic Lymphocytes
Fan, X., Krahling, S., Smith, D. M., Williamson, P., & Schlegel, R. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0670 · Cited by 123
“Apoptotic cells are recognized and phagocytosed by neighboring cells and professional phagocytes in a process that suppresses autoimmune and inflammatory reactions (Fadok et al., 1998).”
BackgroundMcKenna, K. E., Whittaker, S. J., Rhodes, L. E., et al. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06857.x · Cited by 123
Dendritic cells in human aging
AGRAWAL, A., Agrawal, S., & Gupta, S. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.007 · Cited by 122
“…cells results in an antiinflammatory response by inhibiting production of pro-inflammatory cytokines and induction of anti-inflammatory cytokines (Fadok et al, 1998), an impaired uptake and therefore inefficient removal of apoptotic cells by DCs from aged human may result in both inflammation…”
BackgroundKushwah, R., Wu, J., Oliver, J., Jiang, G., Zhang, J., Siminovitch, K. A., & Hu, J. (2010) · European Journal of Immunology · doi:10.1002/eji.200939782 · Cited by 122
Tissue transglutaminase (TG2) - a wound response enzyme
Telci, D. (2006) · Frontiers in bioscience · doi:10.2741/1843 · Cited by 123
“Phagocytosis of apoptotic cells by macrophages induces TGF-beta1 secretion, which would then act as a down-regulator of the pro-inflammatory cytokines (69).”
BackgroundModulation of Neutrophil Apoptosis and the Resolution of Inflammation through β2 Integrins
Kebir, D. E., & Filep, J. G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00060 · Cited by 130
An Antibiotic-Responsive Mouse Model of Fulminant Ulcerative Colitis
Kang, S. S., Bloom, S. M., Norian, L. A., Geske, M. J., Flavell, R. A., Stappenbeck, T. S., & Allen, P. M. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050041 · Cited by 121
“Because both IL-10 and TGFb signaling pathways have been demonstrated to be anti-inflammatory, in part through control of proinflammatory cytokines such as IFNc and TNFa [12–16], we hypothesized that genetic ablation of these two pathways would synergize to elicit more acute pathology than loss of either pathway alone.”
BackgroundHonoré, C., Hummelshøj, T., Hansen, B. E., MADSEN, H. O., Eggleton, P., & Garred, P. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22564 · Cited by 121
Somersan, S., & Bhardwaj, N. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200110066 · Cited by 121
“Under noninflammatory conditions, uptake of ACs by macrophages is thought to suppress autoimmune responses through production of IL-10, TGF , PAF, and PGE 2 and inhibition of TNF , GM-CSF, IL-12, IL-1 , and IL-8 release (Voll et al., 1997; Fadok et al., 1998).”
BackgroundChapman, K. E., Coutinho, A. E., Zhang, Z., Kipari, T. M. J., Savill, J., & Seckl, J. R. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.002 · Cited by 125
Adiponectin in Cardiovascular Inflammation and Obesity
Aprahamian, T. R., & Sam, F. (2011) · International Journal of Inflammation · doi:10.4061/2011/376909 · Cited by 124
“Other functions of M2 macrophages include the ability to upregulate scavenger receptors, mannose receptors, and the IL-1 receptor antagonist [73–75].”
BackgroundThe Role of Macrophages in the Infarcted Myocardium: Orchestrators of ECM Remodeling
O’Rourke, S. A., Dunne, A., & Monaghan, M. G. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00101 · Cited by 124
“M2c macrophages are induced by IL-10 and secrete high levels of transforming growth factor beta 1 (TGFβ1), and glucocorticoids.”
BackgroundInfluentialKosyreva, A. M., Dzhalilova, D. S., Lokhonina, А. V., Vishnyakova, P., & Fatkhudinov, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.682871 · Cited by 122
Reddy, N. M., Potteti, H. R., Mariani, T. J., Biswal, S. S., & Reddy, S. P. (2011) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0144oc · Cited by 120
“They are also essential for the clearance of apoptotic granulocytes and cell debris and the resolution of lung injury and inflammation (33, 34).”
Nakanishi, H., Zhang, J., Koike, M., Nishioku, T., Okamoto, Y., Kominami, E., FIGURA, K. V., Peters, C., Yamamoto, K., Säftig, P., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07526.2001 · Cited by 119
“On the other hand, phagocytosis of opsonized apoptotic cells via the complement receptor type 3 (CR3) has no significant effect on the secretion of pro- or anti-inflammatory cytokines (Fadok et al., 1998).”
BackgroundCD36 and TLR Interactions in Inflammation and Phagocytosis: Implications for Malaria
Erdman, L. K., Cosı́o, G., Helmers, A. J., Gowda, D. C., Grinstein, S., & Kain, K. C. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901374 · Cited by 124
Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide
Reber, L. L., Gillis, C. M., Starkl, P. M., Jönsson, F., Sibilano, R., Marichal, T., Gaudenzio, N., Berard, M., Rogalla, S., Contag, C. H., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161238 · Cited by 125
“Neutrophil death is also thought to contribute importantly to the control and resolution of inflammation, and macrophage uptake of aging or apoptotic neutrophils can dampen the inflammatory responses of the macrophages themselves (Fadok et al., 1998; Poon et al., 2014).”
Li, L., Yang, S., Song, L., Zeng, Y., He, T., Wang, N., Yu, C., Yin, T., Liu, L., Wei, X., et al. (2017) · Theranostics · doi:10.7150/thno.19826 · Cited by 120
“This event is associated with the release of potent anti-inflammatory cytokines like transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2), or platelet-activating factors as a mechanism to avoid immune activation [22-25].”
BackgroundBrain vulnerability and viability after ischaemia
Daniele, S. G., Trummer, G., Hossmann, K. A., Vrselja, Z., Benk, C., Gobeske, K. T., Damjanović, D., Andrijević, D., Pooth, J., Dellal, D., et al. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00488-y · Cited by 125
Leverrier, Y., Lorenzi, R., Blundell, M. P., Brickell, P. M., Kinnon, C., Ridley, A. J., & Thrasher, A. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.4831 · Cited by 119
Svegliati‐Baroni, G., Minicis, S. D., & Marzioni, M. (2008) · Liver International · doi:10.1111/j.1478-3231.2008.01825.x · Cited by 119
Seaton, E. D., Szydlo, R., Kanfer, E., Apperley, J. F., & Russell‐Jones, R. (2003) · Blood · doi:10.1182/blood-2002-11-3351 · Cited by 120
A Critical Role for ABCG1 in Macrophage Inflammation and Lung Homeostasis
Wojcik, A. J., Skaflen, M. D., Srinivasan, S. R., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.4273 · Cited by 119
Matrix-bound nanovesicles recapitulate extracellular matrix effects on macrophage phenotype
Huleihel, L., Bartolacci, J. G., Dziki, J. L., Vorobyov, T., Arnold, B., Scarritt, M. E., Pineda Molina, C., LoPresti, S. T., Brown, B. N., Naranjo, J. D., et al. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0102 · Cited by 116
Macrophage development and polarization in chronic inflammation
Motwani, M. P., & Gilroy, D. W. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.07.002 · Cited by 119
Konduru, N. V., Tyurina, Y. Y., Feng, W., Basova, L., Belikova, N. A., Bayır, H., Clark, K., Rubin, M. A., Stolz, D. B., Vallhov, H., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004398 · Cited by 118
“This interaction triggers not only effective clearance of apoptotic cells but also suppression of the inflammatory response [14,15] or of adaptive immunity [16], thus limiting local tissue responses and normally leading to a quiet cell removal [13].”
BackgroundApoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells
Trahtemberg, U., & Mevorach, D. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01356 · Cited by 125
“Apoptotic cells were shown to downregulate TLR signaling events by us and by other groups, with effects on LPS-TLR4, zymosan-TLR2, and possibly other events (9, 37, 49, 50, 58, 59).”
BackgroundUntargeted effects of ionizing radiation: Implications for radiation pathology
Wright, E. G., & Coates, P. J. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.03.035 · Cited by 119
Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes
Das, A., Ghatak, S., Sinha, M., Chaffee, S. M., Ahmed, N. S., Parinandi, N. L., Wohleb, E. S., Sheridan, J. F., Sen, C. K., & Roy, S. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502270 · Cited by 124
“Successful efferocytosis is known to suppress proinflammatory and upregulate anti-inflammatory genes (30, 45).”
Granuloma Encapsulation Is a Key Factor for Containing Tuberculosis Infection in Minipigs
Gil, O., Díaz, I., Vilaplana, C., Tapia, G., Dı́az, J., Fort, M., Cáceres, N., Pinto, S., Caylà, J. A., Corner, L. A. L., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010030 · Cited by 116
Role of Hyaluronic Acids and Potential as Regenerative Biomaterials in Wound Healing
Yang, H., Song, L., Zou, Y., Sun, D., Wang, L., Yu, Z., & Guo, J. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c01364 · Cited by 124
Čoma, M., Fröhlichová, L., Urban, L., Zajíček, R., Urban, T., Szabó, P., Novak, S., Fetissov, V., Dvořánková, B., Smetana, K., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020897 · Cited by 124
Esmann, L., Idel, C., Sarkar, A., Hellberg, L., Behnen, M., Möller, S., van Zandbergen, G., Klinger, M. H. F., Köhl, J., Bussmeyer, U., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900564 · Cited by 121
“the presence of apoptotic neutrophils (17).”
Requirement for Transforming Growth Factor β1 in Controlling T Cell Apoptosis
Chen, W., Jin, W., Tian, H., Sicurello, P., Frank, M., Orenstein, J. M., & Wahl, S. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.4.439 · Cited by 117
“Resolution of this paradox may rely on a well-known fact that apoptosis and clearing of apoptotic cells are noninflammatory events, involving immunoregulatory cytokines such as TGF- produced by macrophages during their phagocytosis of apoptotic cells (58) to dampen inflammation.”
Alternative activation of macrophages in human peritoneum: implications for peritoneal fibrosis
Bellón, T., Martínez, V., Lucendo, B., del Peso, G., Castro, M. J., Aroeira, L. S., Rodríguez-Sanz, A., Ossorio, M., Sánchez-Villanueva, R., Selgas, R., et al. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq771 · Cited by 114
“CD14(1) purified peripheral blood monocytes were cultured for 96 h in RPMI plus 10% autologous serum at 37 C, 5% CO2 to induce Mu differentiation [6].”
Tsao, L.-C., Crosby, E. J., Trotter, T. N., Agarwal, P., Hwang, B.-J., Acharya, C. R., Shuptrine, C. W., Wang, T., Wei, J.-P., Yang, X. Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.131882 · Cited by 120
“Indeed, several studies have 468 demonstrated that cellular phagocytosis over time influences macrophage phenotype, causing a 469 switch from pro-inflammatory to a growth promoting, reparative phenotype (44-46).”
BackgroundBiodistribution and clearance of instilled carbon nanotubes in rat lung
Elgrabli, D., Floriani, M., Abella-Gallart, S., Meunier, L., Gamez, C., Delalain, P., Rogerieux, F., Boczkowski, J., & Lacroix, G. (2008) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-5-20 · Cited by 117
“This elimination was demonstrated to be in pair with the inhibition of IL10 and GM-CSF protein and absence of inflammation [21].”
Wang, Z., Larregina, A. T., Shufesky, W. J., Perone, M. J., Montecalvo, A., Zahorchak, A. F., Thomson, A. W., & Morelli, A. E. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01308.x · Cited by 116
“cells originated from stressed (33) or pathogen-infected cells (29,34) or (ii) IgG-opsonized apoptotic cells (35).”
BackgroundTransforming Growth Factor-β1-Mediated Neuroprotection against Excitotoxic Injury in Vivo
Boche, D., Cunningham, C. M., Gauldie, J., & Perry, V. H. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000090080.64176.44 · Cited by 115
APOPTOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Andrade, F., Casciola-Rosen, L. A., & Rosen, A. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70136-8 · Cited by 115
Ward, C., Dransfield, I., Murray, J., Farrow, S. N., Haslett, C., & Rossi, A. G. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.12.6232 · Cited by 115
Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an Antiviral Mechanism
Nainu, F., Shiratsuchi, A., & Nakanishi, Y. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01220 · Cited by 120
Metadata
- Authors
- Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M.
- Affiliations
- National Jewish Health (US)
- ORCID
- Henson, P M
- Venue
- Journal of Clinical Investigation
- Published
- 1998-02-15
- Volume
- 101
- Issue
- 4
- Pages
- 890-898
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508637
- OpenAlex
- W2095537212
- Semantic Scholar
- 3e88d8a52759097d481b92ec0d06606afbadafab
- Cited by
- 3,166
- References
- 50
- Citations by year
- 2026: 60 · 2025: 74 · 2024: 91 · 2023: 82 · 2022: 91 · 2021: 129 · 2020: 114 · 2019: 125 · 2018: 106 · 2017: 113 · 2016: 117 · 2015: 109 · 2014: 116 · 2013: 130 · 2012: 133
- FWCI
- 29.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL34303, P01HL034303)
- National Institute of General Medical Sciences (GM48211, R01GM048211)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- phagocytosis of apoptotic cells, macrophages, inflammation resolution, anti-inflammatory macrophages, inflammatory cytokines, TGF-β1, prostaglandin E2, platelet-activating factor, autocrine and paracrine signaling, neutrophil apoptosis, monocyte-derived macrophages, indomethacin, PAF receptor antagonists
- MeSH terms
- Humans, Inflammation, Macrophages, Neutrophils, Phagocytosis, Platelet Activating Factor, Solubility, Thromboxane B2, Dinoprostone, Cytokines, Transforming Growth Factor beta, Apoptosis, Leukotriene C4, Jurkat Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
