CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair
Open accessAbstract
Monocytes/macrophages are critical in orchestrating the tissue-repair response. However, the mechanisms that govern macrophage regenerative activities during the sequential phases of repair are largely unknown. In the present study, we examined the dynamics and functions of diverse monocyte/macrophage phenotypes during the sequential stages of skin repair. By combining the analysis of a new CCR2-eGFP reporter mouse model with conditional mouse mutants defective in myeloid cell-restricted CCR2 signaling or VEGF-A synthesis, we show herein that among the large number of inflammatory CCR2(+)Ly6C(+) macrophages that dominate the early stage of repair, only a small fraction strongly expresses VEGF-A that has nonredundant functions for the induction of vascular sprouts. The switch of macrophage-derived VEGF-A during the early stage of tissue growth toward epidermal-derived VEGF-A during the late stage of tissue maturation was critical to achieving physiologic tissue vascularization and healing progression. The results of the present study provide new mechanistic insights into CCR2-mediated recruitment of blood monocyte subsets into damaged tissue, the dynamics and functional consequences of macrophage plasticity during the sequential repair phases, and the complementary role of macrophage-derived VEGF-A in coordinating effective tissue growth and vascularization in the context of tissue-resident wound cells. Our findings may be relevant for novel monocyte-based therapies to promote tissue vascularization.
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Recent studies have shown that macrophage phenotypes change over the different phases of tissue repair and that the sequential appearance of these phenotypes may be required for efficient repair.
“Recent studies have shown that Mp phenotypes change over the different phases of tissue repair and that the sequential appearance of these phenotypes may be required for efficient repair (11,14,29,49,50).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [11]
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Organ-Level Quorum Sensing Directs Regeneration in Hair Stem Cell Populations
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“Macrophages can be divided into two major types; M1 macrophages (classi- cally activated) exert proinflammatory activities, and M2 macrophages (alternatively activated) are involved in resolving inflammation (Gordon, 2003; Willenborg et al., 2012).”
Targeting epigenetic mechanisms in diabetic wound healing
den Dekker, A. D., Davis, F. M., Kunkel, S. L., & Gallagher, K. A. (2018) · Translational research · doi:10.1016/j.trsl.2018.10.001 · Cited by 238 · see citing works
“During the normal healing process, macrophages are initially proinflammatory and then transition to an anti-inflammatory phenotype where they promote tissue repair and transition to the next phase of healing.(6,8,9) In diabetic wounds, however, this macrophage transition is altered, causing them to remain in a proinfl…”
Olingy, C. E., Emeterio, C. L. S., Ogle, M. E., Krieger, J. R., Bruce, A. C., Pfau, D. D., Jordan, B. T., Peirce, S. M., & Botchwey, E. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-00477-1 · Cited by 226 · see citing works
“The unique protein signature of non-classical monocytes, characterized by higher VEGF, TGF β , and IL-10, and lower TNF α and IL-1 β expression compared to classical monocytes has resulted in the suggestion that these cells may constitute a class of “anti-inflammatory” monocytes 18, 19 .”
BackgroundInfluentialDisclosure of the culprits: macrophages-versatile regulators of wound healing.
Sindrilaru, A., & Scharffetter-Kochanek, K. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0407 · Cited by 223 · see citing works
“In contrast, the absence of Ly6CCCR2 inflammatory monocytes/macrophages in myeloid-restricted CCR2 deficient mice did not affect overall wound closure despite impairing the early phases of neovascularisation and myofibroblast differentiation.(20) Thus, the early recruitment of Ly6CCCR2 monocytes may reflect an evoluti…”
BackgroundMethodTranscriptome analysis of IL-10-stimulated (M2c) macrophages by next-generation sequencing
Lurier, E., Dalton, D., Dampier, W., Raman, P., Nassiri, S., Ferraro, N., Rajagopalan, R., Sarmady, M., & Spiller, K. (2017) · Immunobiology · doi:10.1016/j.imbio.2017.02.006 · Cited by 204 · see citing works
Niu, Y., Wang, Z., Shi, Y., Dong, L., & Wang, C. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.08.012 · Cited by 213 · see citing works
Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization
Zhang, S.-Q., Liu, Y.-Y., Zhang, X., Zhu, D.-S., Qi, X., Cao, X.-C., Fang, Y., Che, Y.-Z., Han, Z.-B., He, Z.-X., et al. (2018) · Theranostics · doi:10.7150/thno.27385 · Cited by 178 · see citing works
“Numerous studies have shown that macrophages are involved in the regulation of angiogenesis during tissue repair [32-36].”
BackgroundRamírez‐Valle, F., Gray, E. E., & Cyster, J. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508990112 · Cited by 211 · see citing works
“C-C chemokine receptor type 2 (CCR2) plays a role in homing of macrophages to inflamed skin and is present on dermal γδT cells (3, 26, 27).”
BackgroundKimball, A., Schaller, M. A., Joshi, A., Davis, F. M., denDekker, A. D., Boniakowski, A. E., Bermick, J., Obi, A. T., Moore, B. B., Henke, P. K., et al. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.310703 · Cited by 212 · see citing works
Clark, A. Y., Martin, K. E., García, J. R., Johnson, C. T., Theriault, H. S., Han, W. M., Zhou, D. W., Botchwey, E. A., & Garcı́a, A. J. (2020) · Nature Communications · doi:10.1038/s41467-019-14000-9 · Cited by 208 · see citing works
Wang, X.-S., Chen, H.-Y., Tian, R.-Y., Zhang, Y., Drutskaya, M., Wang, C., Ge, J.-F., Fan, Z., Kong, D., Wang, X.-X., et al. (2017) · Nature Communications · doi:10.1038/ncomms14091 · Cited by 208 · see citing works
Altered macrophage phenotype transition impairs skeletal muscle regeneration.
Wang, H.-Z., Melton, D., Porter, L., Sarwar, Z. U., McManus, L., & Shireman, P. (2014) · American Journal of Pathology · doi:10.1016/j.ajpath.2013.12.020 · Cited by 189 · see citing works
“The American Journal of Pathology based on the cytokine and chemokines production anticipated from M1 macrophages such as IL-1a,46,47 MCP-1,48 51 MCP-3,50,51 MIP-2,3 OSM,52 TNFa,7,47,49,53 and VEGF.5,54 The additional cytokines that were significantly elevated in the Ly6CþCD301 (FGF9, lymphotactin, and SCF) are not co…”
MethodImage based Machine Learning for identification of macrophage subsets
Rostam, H. M., Reynolds, P. M., Alexander, M. R., Gadegaard, N., & Ghaemmaghami, A. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-03780-z · Cited by 196 · see citing works
“These cells have also been shown to express high levels of chemokine (C-C motif) receptor 7 (CCR7) 17 , nitric oxide synthase 2 (NOS2) 18 , calprotectin 19 , and CCR2 20 .”
BackgroundCD11b + Ly6G − myeloid cells mediate mechanical inflammatory pain hypersensitivity
Ghasemlou, N., Chiu, I. M., Julien, J., & Woolf, C. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501372112 · Cited by 189 · see citing works
“Nonneutrophil myeloid cells are primarily responsible for the phagocytosis of debris and invading pathogens in incisional wounds, and, although they are not required for tissue repair, they do play important roles in vascularization, fibrosis, and scarring (37, 68, 69).”
BackgroundCD301b+ Macrophages Are Essential for Effective Skin Wound Healing
Shook, B. A., Xiao, E.-C., Kumamoto, Y., Iwasaki, A., & Horsley, V. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.107 · Cited by 167 · see citing works
“After injury, CD11b+/F4-80+ macrophages are recruited to skin in a CCR2-dependent manner and express high levels of Ly6C (Ly6Chi) (Ramachandran et al., 2012; Rodero et al., 2012; Willenborg et al., 2012) and inflammatory cytokines (Eming et al., 2007; Werner and Grose, 2003).”
Macrophages are necessary for epimorphic regeneration in African spiny mice
Simkin, J., Gawriluk, T. R., Gensel, J. C., & Seifert, A. W. (2017) · eLife · doi:10.7554/elife.24623 · Cited by 190 · see citing works
“Whereas CD206+ cells were absent from the blastema in Acomys, in Mus, we observed CD206+ cells throughout the collagen-rich granulation tissue, a situation similar to fibrosis observed during skin wound repair (Mirza and Koh, 2011; Song et al., 2000; Willenborg et al., 2012).”
BackgroundMia, M. M., Cibi, D. M., Ghani, S. A. B. A., Song, W., Tee, N., Ghosh, S., Mao, J., Olson, E. N., & Singh, M. K. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000941 · Cited by 183 · see citing works
“Using a reporter mouse line, Willenborg and colleagues demonstrated that Vegf expression by macrophages is required to induce capillary sprouting during wound healing [73].”
BackgroundWound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities
Bukowiecki, A., Hos, D., Cursiefen, C., & Eming, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061257 · Cited by 174 · see citing works
“recruitment of VEGF-A-expressing macrophages is critical for the initiation of capillary sprouting during the wound healing response [174].”
BackgroundOvermeire, E. V., Laoui, D., Keirsse, J., Ginderachter, J. A. V., & Sarukhan, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00127 · Cited by 182 · see citing works
“This is expected to be especially prominent under (chronic) inflammatory conditions and injury, during which the tissue macrophage pool is typically reinforced by the influx of monocytes, as demonstrated in liver (34), skin (35, 36), brain (37), colon (38), and other tissues.”
BackgroundSaldaña, L., Bensiamar, F., Vallés, G., Mancebo, F. J., García‐Rey, E., & Vilaboa, N. E. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1156-6 · Cited by 172 · see citing works
Differential gene expression in human, murine, and cell line-derived macrophages upon polarization
Spiller, K. L., Wrona, E. A., Romero‐Torres, S., Pallotta, I., Graney, P. L., Witherel, C. E., Panicker, L. M., Feldman, R. A., Urbanska, A. M., Santambrogio, L., et al. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.10.017 · Cited by 172 · see citing works
“6 phenotype promoting angiogenesis [19, 20], while other studies have shown that M1 macrophages are more angiogenic [16, 21].”
BackgroundMacrophage Dysregulation and Impaired Skin Wound Healing in Diabetes
Barman, P., & Koh, T. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00528 · Cited by 152 · see citing works
“In addition, wound Mo/Mφ are an important source of growth factors such as VEGF, which is critical for angiogenesis and tissue growth (Stockmann et al., 2011; Willenborg et al., 2012).”
BackgroundHsieh, C. L., Niemi, E. C., Wang, S. H., Lee, C. C., Bingham, D., Zhang, J., Cozen, M. L., Charo, I., Huang, E. J., Liu, J., et al. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3252 · Cited by 174 · see citing works
Jacome-Galarza, C. E., Lee, S., Lorenzo, J., & Aguila, H. L. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1822 · Cited by 155 · see citing works
IL-4 and IL-13: Regulators and Effectors of Wound Repair
Allen, J. E. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-041206 · Cited by 151 · see citing works
Monocyte-endothelial cell interactions in vascular and tissue remodeling
Medrano-Bosch, M., Simón-Codina, B., Jiménez, W., Edelman, E., & Melgar-Lesmes, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1196033 · Cited by 148 · see citing works
Okizaki, S.-I., Ito, Y., Hosono, K., Oba, K., Ohkubo, H., Amano, H., Shichiri, M., & Majima, M. (2015) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2014.10.020 · Cited by 145 · see citing works
Role of Macrophages in Wound HealingPreprint
Willenborg, S., Injarabian, L., & Eming, S. A. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041216 · Cited by 147 · see citing works
Awojoodu, A. O., Ogle, M. E., Sefcik, L. S., Bowers, D. T., Martin, K. S., Brayman, K. L., Lynch, K. R., Peirce, S. M., & Botchwey, E. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221309110 · Cited by 147 · see citing works
“Similarly, in the spinotrapezius model in vessels surrounding FTY720-loaded PLAGA scaffolds in ischemic muscle, there was a significant increase in cells expressing CX3CR1, possibly owing to increased SDF-1α in response to ischemia (25).”
BackgroundResultOsteomacs and Bone Regeneration
Batoon, L., Millard, S. M., Raggatt, L. J., & Pettit, A. R. (2017) · Current Osteoporosis Reports · doi:10.1007/s11914-017-0384-x · Cited by 146 · see citing works
The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited
Dzobo, K., Senthebane, D. A., & Dandara, C. (2023) · Cancers · doi:10.3390/cancers15020376 · Cited by 146 · see citing works
Bannon, P., Wood, S., Restivo, T., Campbell, L., Hardman, M., & Mace, K. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.012237 · Cited by 154 · see citing works
“Recent studies suggest that CCR2+ M1/M2 mixed-phenotype myeloid cells make up the majority of pro-angiogenic macrophages during wound healing and, consistent with our data, are present at early wound time points (Willenborg et al., 2012).”
Wermuth, P. J., & Jiménez, S. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0047-4 · Cited by 151 · see citing works
“numbers with a concomitant increase of Ly6C monocytes [17-24].”
BackgroundKim, Y., Furuya, H., & Tabata, Y. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.09.103 · Cited by 140 · see citing works
“The deficiency of macrophages at tissue defects delayed the process of the tissue regeneration because macrophages play a important role in the phagocytosis or removal of pathogen and initiation of relative gene expression for tissues repairing [11, 49].”
BackgroundCCL17 Aggravates Myocardial Injury by Suppressing Recruitment of Regulatory T Cells
Feng, G., Bajpai, G., Ma, P., Koenig, A. L., Bredemeyer, A. L., Lokshina, I., Lai, L., Förster, I., Leuschner, F., Kreisel, D., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.055888 · Cited by 140 · see citing works
Mantsounga, C., Lee, C. F., Neverson, J., Sharma, S., Healy, A. L., Berus, J. M., Parry, C., Ceneri, N. M., López‐Giráldez, F., Chun, H. J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110309 · Cited by 139 · see citing works
“In humans, this inflammatory macrophage population is characterized by the high expression of the chemokine receptor, C-C motif chemokine receptor 2 (CCR2), and the lipopolysaccharide (LPS) co-receptor, CD14, inducible nitric oxide synthase (NOS2), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6) (Willenborg et al.…”
InfluentialNakkala, J. R., Li, Z., Ahmad, W., Wang, K., & Gao, C. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.025 · Cited by 136 · see citing works
Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds
Freudenberg, U., Zieris, A., Chwalek, K., Tsurkan, M. V., Maitz, M. F., Atallah, P., Levental, K. R., Eming, S. A., & Werner, C. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.028 · Cited by 128 · see citing works
He, L.-Z., & Marneros, A. G. (2013) · American Journal of Pathology · doi:10.1016/j.ajpath.2013.02.032 · Cited by 132 · see citing works
“Efficient Cremediated excision of the floxed VEGF-A allele in myeloid cells with lysozyme M Cre mice has been demonstrated.(17,18) Cre expression in RPE cells that are homozygous for the floxed VEGF-A was assessed by immunolabeling for Cre using a monoclonal mouse antiCre antibody (clone 2D8; EMD Millipore, Billerica,…”
MethodResultInfluentialBoniakowski, A. E., Kimball, A., Joshi, A. D., Schaller, M., Davis, F. M., denDekker, A., Obi, A., Moore, B., Kunkel, S., & Gallagher, K. (2018) · European Journal of Immunology · doi:10.1002/eji.201747400 · Cited by 109 · see citing works
Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory
Geng, K., Ma, X., Jiang, Z., Huang, W. G., Gao, C., Pu, Y., Luo, L., Xu, Y., & Xu, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.653940 · Cited by 121 · see citing works
Sidibé, A., Ropraz, P., Jemelin, S., Emre, Y., Poittevin, M., Pocard, M. D., Bradfield, P. F., & Imhof, B. A. (2018) · Nature Communications · doi:10.1038/s41467-017-02610-0 · Cited by 116 · see citing works
Little, K., Jacey, H., Yang, N., Chen, M., & Xu, H. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.029 · Cited by 117 · see citing works
“For example, RPE, microglia and macrophages can all produce CCL2, a chemokine that plays an important role in the recruitment of CCR2 macrophages [48] and fibrocytes [49].”
BackgroundThe impact of surface chemistry modification on macrophage polarisation
Rostam, H. M., Singh, S., Salazar, F., Magennis, E. P., Hook, A. L., Singh, T., Vrana, N. E., Alexander, M. R., & Ghaemmaghami, A. M. (2016) · Immunobiology · doi:10.1016/j.imbio.2016.06.010 · Cited by 116 · see citing works
The Role of Macrophages in Skin Homeostasis
Yanez, D. A., Lacher, R. K., Vidyarthi, A., & Colegio, O. (2017) · Pflügers Archiv: European Journal of Physiology · doi:10.1007/s00424-017-1953-7 · Cited by 102 · see citing works
“Moreover, phagocytosis of apoptotic cells by macrophages leads to the production of VEGF-A [17], which induces vascularization and tissue regeneration [77].”
Toll-Like Receptor Function in Acute Wounds
Chen, L., & DiPietro, L. (2017) · Advances in wound care · doi:10.1089/wound.2017.0734 · Cited by 102 · see citing works
“reaction, help recruit more inflammatory cells, and promote the proliferative phase of repair, including angiogenesis and tissue regrowth.(19,24,25) Multiple studies now demonstrate that macrophages play an indispensable role in wound healing.”
Burgess, M. O., Wicks, K., Gardasevic, M., & Mace, K. A. (2019) · ImmunoHorizons · doi:10.4049/immunohorizons.1900038 · Cited by 114 · see citing works
“Our results support previous analyses of classically activated and alternatively activated macrophages in skin in which CCR2 macrophages recruited from BM were the predominant macrophage subtype present and initially showed a classically activated phenotype, playing a critical role during the early inflammatory stages…”
ResultLaurent, F., & Lacroix‐Lamandé, S. (2017) · International Journal for Parasitology · doi:10.1016/j.ijpara.2017.08.001 · Cited by 112 · see citing works
“However, in addition to impaired recruitment via CCR2, CCR2-/-mice exhibit impaired egress of Ly6c+ monocytes from the bone marrow (Egan et al., 2009; Platt et al., 2010; Willenborg et al., 2012).”
BackgroundPedragosa, J., Miró‐Mur, F., Otxoa-de-Amezaga, A., Justicia, C., Ruíz-Jaén, F., Ponsaerts, P., Pasparakis, M., & Planas, A. M. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20909055 · Cited by 112 · see citing works
“CCR2-deficiency in monocytes reduces monocyte infiltration to the ischemic brain tissue without affecting the recruitment of other leukocytes To investigate the function of infiltrating CCR2þ monocytes we induced selective CCR2 deletion in myeloid cells by crossing LysMcreþ mice with floxed Ccr2 (Ccr2) mice (Figure 2(…”
BackgroundMethodInfluentialPlatelet Derivatives and the Immunomodulation of Wound Healing
Scopelliti, F., Cattani, C., Martino, V. D., Mirisola, C., & Cavani, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158370 · Cited by 97 · see citing works
Jiang, D.-S., Qi, Y., Walker, N., Sindrilaru, A., Hainzl, A., Wlaschek, M., MacNeil, S., & Scharffetter-Kochanek, K. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2012.12.014 · Cited by 117 · see citing works
Temporal changes in macrophage phenotype after peripheral nerve injury
Tomlinson, J. E., Žygelytė, E., Grenier, J. K., Edwards, M. G., & Cheetham, J. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1219-0 · Cited by 110 · see citing works
Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings
Alhamdi, J. R., Peng, T., Al-Naggar, I. M., Hawley, K. L., Spiller, K. L., & Kuhn, L. T. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.012 · Cited by 110 · see citing works
“Furthermore, given the ability of M1 macrophages to s imulate angiogenesis during tissue regeneration (78, 79), the enhanced M1 macrophage p henotype induced by the bCaP coating may contribute positively to tissue repair.”
Rehak, L., Giurato, L., Meloni, M., Panunzi, A., Manti, G. M., & Uccioli, L. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030889 · Cited by 111 · see citing works
“During this phase, both M1 and M2 are also responsible for the vascularization process, first creating new vessels trough sprouting [40], then creating anastomoses between newly formed vessels [41].”
BackgroundModelling skin wound healing angiogenesis: A review
Guerra, A., Belinha, J., & Jorge, R. N. (2018) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2018.09.020 · Cited by 108 · see citing works
Macrophage regulation of angiogenesis in health and disease.
Martin, P., & Gurevich, D. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.06.010 · Cited by 102 · see citing works
“These macrophages express high levels of typically pro-inflammatory M1 markers, IL6 and iNOS, but also expressed the more anti-inflammatory M2 related TIE2 receptor [9].”
BackgroundA monocyte–leptin–angiogenesis pathway critical for repair post-infection
Kratofil, R. M., Shim, H. B., Shim, R., Lee, W.-Y., Labit, E., Sinha, S., Keenan, C. M., Surewaard, B. G. J., Noh, J. Y., Sun, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-05044-x · Cited by 105 · see citing works
In Situ Tissue Engineering of Functional Small-Diameter Blood Vessels by Host Circulating Cells Only
Talacua, H., Smits, A. I. P. M., Muylaert, D. E. P., van Rijswijk, J. W., Vink, A., Verhaar, M. C., Driessen‐Mol, A., van Herwerden, L. A., Bouten, C. V. C., Kluin, J., et al. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2015.0066 · Cited by 104 · see citing works
“8,26,27 Monocyte and macrophage trafficking was shown to be dependent on MCP-1 and its primary receptor, CCR2.”
Endothelial progenitor cell: a blood cell by many other names may serve similar functions
Yöder, M. C. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1002-8 · Cited by 104 · see citing works
“A sampling of recent work reveals that different monocyte subsets appear more readily specified to proangiogenic macrophage fates [114–116], are key components of the tumor microenvironment [117, 118], can be targeted for specific antitumor angiogenic responses [119–121], employ both Wnt [122] and Notch [123–125] sign…”
BackgroundRodriguez-Menocal, L., Shareef, S., Salgado, M., Shabbir, A., & Badiavas, E. V. (2015) · Stem Cell Research & Therapy · doi:10.1186/s13287-015-0001-9 · Cited by 102 · see citing works
“Some reports suggest that certain bone marrow derived cells, such as mesenchymal stem cells, secrete a broad spectrum of angiogenic or anti-apoptotic cytokines, which play a role in the process of tissue repair and that BMMSC conditioned medium has been shown to contain the majority of human cytokines fundamental in w…”
BackgroundNotch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing
Kimball, A., Joshi, A., Boniakowski, A. E., Schaller, M. A., Chung, J., Allen, R., Bermick, J., Carson, W. F., Henke, P. K., Maillard, I. P., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00635 · Cited by 101 · see citing works
“For example, canonical Notch signaling and vascular endothelial growth factor-A (VEGF-A) are known to play a role in angiogenesis in both tumors and injured tissue, while simultaneously VEGF-A is known to be secreted by infiltrating inflammatory monocytes (25, 43, 44).”
Background
- Authors
- Willenborg, S., Lucas, T., van Loo, G., Knipper, J. A., Krieg, T., Haase, I., Brachvogel, B., Hammerschmidt, M., Nagy, A., Ferrara, N., Pasparakis, M., & Eming, S. A.
- Affiliations
- University of Cologne (DE)
- Department for Molecular Biomedical Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium;
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON;
- Genentech (US)
- Corresponding author
- Willenborg, Sebastian
- Lucas, Tina
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-07-19
- Volume
- 120
- Issue
- 3
- Pages
- 613-625
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2065145765
- Cited by
- 534
- References
- 40
- Citations by year
- 2026: 29 · 2025: 43 · 2024: 38 · 2023: 55 · 2022: 46 · 2021: 40 · 2020: 40 · 2019: 34 · 2018: 38 · 2017: 43 · 2016: 32 · 2015: 29 · 2014: 37 · 2013: 24 · 2012: 5
- FWCI
- 32.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- European Commission (2007–2013, 214402)
- Deutsche Forschungsgemeinschaft
- Universiteit Gent
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- CCR2, macrophage plasticity, VEGF-A, angiogenesis, skin wound healing, tissue repair, monocyte recruitment, vascular sprouting, tissue vascularization
- MeSH terms
- Animals, Cells, Cultured, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Regeneration, Skin, Wound Healing, Signal Transduction, Macrophages, Peritoneal, Neovascularization, Physiologic, Gene Expression Profiling, Myeloid Cells, Vascular Endothelial Growth Factor A, Green Fluorescent Proteins, Mice, Receptors, CCR2
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