S100A9 Differentially Modifies Phenotypic States of Neutrophils, Macrophages, and Dendritic Cells: Implications for Atherosclerosis and Adipose Tissue Inflammation
Open accessAbstract
Background—: S100A9 is constitutively expressed in neutrophils, dendritic cells, and monocytes; is associated with acute and chronic inflammatory conditions; and is implicated in obesity and cardiovascular disease in humans. Most of the constitutively secreted S100A9 is derived from myeloid cells. A recent report demonstrated that mice deficient in S100A9 exhibit reduced atherosclerosis compared with controls and suggested that this effect was due in large part to loss of S100A9 in bone marrow–derived cells. Methods and Results—: To directly investigate the role of bone marrow–derived S100A9 in atherosclerosis and insulin resistance in mice, low-density lipoprotein receptor–deficient, S100A9-deficient bone marrow chimeras were generated. Neither atherosclerosis nor insulin resistance was reduced in S100A9-deficient chimeras fed a diet rich in fat and carbohydrates. To investigate the reason for this lack of effect, myeloid cells were isolated from the peritoneal cavity or bone marrow. S100A9-deficient neutrophils exhibited a reduced secretion of cytokines in response to toll-like receptor-4 stimulation. In striking contrast, S100A9-deficient dendritic cells showed an exacerbated release of cytokines after toll-like receptor stimulation. Macrophages rapidly lost S100A9 expression during maturation; hence, S100A9 deficiency did not affect the inflammatory status of macrophages. Conclusions—: S100A9 differentially modifies phenotypic states of neutrophils, macrophages, and dendritic cells. The effect of S100A9 deficiency on atherosclerosis and other inflammatory diseases is therefore predicted to depend on the relative contribution of these cell types at different stages of disease progression. Furthermore, S100A9 expression in nonmyeloid cells is likely to contribute to atherosclerosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
HLAhiS100lo cDC2s were enriched in antigen-presenting genes, whereas S100hiHLAlo cDC2s enriched for regulatory genes including TGFBR1 and S100A9, reported to suppress DC cytokine production.
“Although the HLAhiS100lo cDC2 cluster was enriched in antigen-presenting genes, S100hiHLAlo cDC2s enriched for regulatory genes, including TGFBR1 and S100A9, were reported to suppress DC cytokine production29 (Fig. 4c,d).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760 · see citing works
Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · see citing works
Self-citationCheng, P., Corzo, C. A., Luetteke, N., Yu, B., Nagaraj, S., Bui, M. M., Ortiz, M. L., Nacken, W. K. F., Sorg, C., Vogl, T., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080132 · Cited by 904 · see citing works
Self-citationRammes, A., Roth, J., Goebeler, M., Klempt, M., Hartmann, M., & Sorg, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.9496 · Cited by 547 · see citing works
Self-citationYao, D., & Brownlee, M. (2009) · Diabetes · doi:10.2337/db09-0801 · Cited by 526 · see citing works
Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding
Elgazar-Carmon, V., Rudich, A., Hadad, N., & Lévy, R. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800132-jlr200 · Cited by 488 · see citing works
Saberi, M., Woods, N.-B., de Luca, C., Schenk, S., Lu, J. C., Bandyopadhyay, G., Verma, I. M., & Olefsky, J. M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.006 · Cited by 456 · see citing works
Labeur, M. S., Roters, B., Pers, B., Mehling, A., Luger, T. A., Schwarz, T., & Grabbe, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.1.168 · Cited by 423 · see citing works
Inflammation-associated S100 proteins: new mechanisms that regulate function
Goyette, J., & Geczy, C. L. (2010) · Amino Acids · doi:10.1007/s00726-010-0528-0 · Cited by 346 · see citing works
Manitz, M., Horst, B. A. J., Seeliger, S., Strey, A., Skryabin, B., Gunzer, M., Frings, W., Schönlau, F., Roth, J., Sorg, C., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.1034-1043.2003 · Cited by 343 · see citing works
Self-citationHealy, A. M., Pickard, M. D., Pradhan, A. D., Wang, Y., Chen, Z., Croce, K., Sakuma, M., Shi, C., Zago, A. C., Garasic, J. M., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.607333 · Cited by 333 · see citing works
Sunahori, K., Yamamura, M., Yamana, J., Takasugi, K., Kawashima, M., Yamamoto, H., Chazin, W., Nakatani, Y., Yui, S., & Makino, H. (2006) · Arthritis Research & Therapy · doi:10.1186/ar1939 · Cited by 324 · see citing works
Boyd, J. H., Kan, B., Roberts, H., Wang, Y., & Walley, K. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.167544 · Cited by 292 · see citing works
Myeloid-Related Protein-8/14 Is Critical for the Biological Response to Vascular Injury
Croce, K., Gao, H., Wang, Y., Mooroka, T., Sakuma, M., Shi, C., Sukhova, G. K., Packard, R. R. S., Hogg, N., Libby, P., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.814582 · Cited by 254 · see citing works
Renard, C. B., Kramer, F., Johansson, F., Lamharzi, N., Tannock, L. R., von Herrath, M. G., Chait, A., & Bornfeldt, K. (2004) · Journal of Clinical Investigation · doi:10.1172/jci17867 · Cited by 228 · see citing works
Self-citationAltwegg, L. A., Neidhart, M., Hersberger, M., Muller, S., Eberli, F. R., Corti, R., Roffi, M., Sütsch, G., Gay, S., von Eckardstein, A., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm078 · Cited by 200 · see citing works
Ehlermann, P., Eggers, K. M., Bierhaus, A., Most, P., Weichenhan, D., Greten, H. J., Nawroth, P. P., Katus, H. A., & Remppis, A. B. (2006) · Cardiovascular Diabetology · doi:10.1186/1475-2840-5-6 · Cited by 198 · see citing works
Renard, C. B., Kramer, F., Johansson, F., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200417867 · Cited by 187 · see citing works
Subramanian, S., Han, C. Y., Chiba, T., McMillen, T. S., Wang, S. A., Haw, A., Kirk, E. A., O’Brien, K. D., & Chait, A. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.157685 · Cited by 182 · see citing works
Kerkhoff, C., Nacken, W. K. F., Benedyk‐Machaczka, M., Dagher, M., Sopalla, C., & Doussière, J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2377fje · Cited by 178 · see citing works
Self-citationGM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions
Zhu, S.-N., Chen, M., Jongstra‐Bilen, J., & Cybulsky, M. I. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090866 · Cited by 166 · see citing works
Morrow, D. A., Wang, Y., Croce, K., Sakuma, M., Sabatine, M. S., Gao, H., Pradhan, A. D., Healy, A. M., Buros, J., McCabe, C. H., et al. (2007) · American Heart Journal · doi:10.1016/j.ahj.2007.08.018 · Cited by 165 · see citing works
Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice.
Rotzius, P., Thams, S., Soehnlein, O., Kenne, E., Tseng, C.-N., Björkström, N., Malmberg, K., Lindbom, L., & Eriksson, E. (2010) · American Journal of Pathology · doi:10.2353/ajpath.2010.090480 · Cited by 162 · see citing works
Viemann, D., Barczyk, K., Vogl, T., Fischer, U., Sunderkötter, C. H., Schulze‐Osthoff, K., & Roth, J. (2006) · Blood · doi:10.1182/blood-2006-08-040444 · Cited by 144 · see citing works
Lagasse, E., & Weissman, I. (1992) · Blood · doi:10.1182/blood.v79.8.1907.1907 · Cited by 140 · see citing works
Expression of myeloid‐related proteins 8 and 14 in systemic‐onset juvenile rheumatoid arthritis
Frosch, M., Vogl, T., Seeliger, S., Wulffraat, N. M., Kuis, W., Viemann, D., Foell, D., Sorg, C., Sunderkötter, C. H., & Roth, J. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11177 · Cited by 136 · see citing works
Self-citationExpression and Role of Myeloid-related Protein-14 in Clinical and Experimental Sepsis
van Zoelen, M. A. D., Vogl, T., Foell, D., van Veen, S. Q., van Till, J. W. O., Florquin, S., Tanck, M. W. T., Wittebole, X., Laterre, P., Boermeester, M. A., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200810-1552oc · Cited by 130 · see citing works
Calprotectin — A Novel Marker of Obesity
Mortensen, O. H., Nielsen, A. R., Erikstrup, C., Plomgaard, P., Fischer, C. P., Krogh‐Madsen, R., Lindegaard, B., Petersen, A. M. W., Taudorf, S., & Pedersen, B. K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007419 · Cited by 118 · see citing works
Ionita, M. G., Vink, A., Dijke, E., Laman, J. D., Peeters, W., van der Kraak, P. H., Moll, F. L., de Vries, J. P. P. M., Pasterkamp, G., & de Kleijn, D. P. V. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.190314 · Cited by 102 · see citing works
Askari, B., Kanter, J. E., Sherrid, A. M., Golej, D. L., Bender, A. T., Liu, J., Hsueh, W. A., Beavo, J. A., Coleman, R., & Bornfeldt, K. (2007) · Diabetes · doi:10.2337/db06-0267 · Cited by 99 · see citing works
Self-citationYen, T., Harrison, C. A., Devery, J. M., et al. (1997) · Blood · doi:10.1182/blood.v90.12.4812 · Cited by 96 · see citing works
Yen, T., Harrison, C. A., Devery, J. M., et al. (1997) · Blood · doi:10.1182/blood.v90.12.4812.4812_4812_4821 · Cited by 87 · see citing works
IL-10 Up-Regulates Macrophage Expression of the S100 Protein S100A8
Xu, K., Yen, T., & Geczy, C. L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.10.6358 · Cited by 83 · see citing works
A Macrophage Sterol-Responsive Network Linked to Atherogenesis
Becker, L., Gharib, S. A., Irwin, A. D., Wijsman, E. M., Vaisar, T., Oram, J. F., & Heinecke, J. W. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.01.003 · Cited by 79 · see citing works
Self-citationRegulation of S100A8 by Glucocorticoids1
Hsu, K. J., Passey, R., Endoh, Y., Rahimi, F., Youssef, P., Yen, T., & Geczy, C. (2005) · Journal of Immunology · doi:10.4049/jimmunol.174.4.2318 · Cited by 65 · see citing works
Schnekenburger, J., Schick, V., Krüger, B., Manitz, M. P., Sorg, C., Nacken, W. K. F., Kerkhoff, C., Kahlert, A., Mayerle, J. V., Domschke, W., et al. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21433 · Cited by 64 · see citing works
Self-citationInaba, H., Hokamura, K., Nakano, K., et al. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.11.036 · Cited by 58 · see citing works
Bouma, G., Coppens, J. M. C., Lam-Tse, W.-K., et al. (2005) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2005.02865.x · Cited by 42 · see citing works
Interleukin-10 Influences the Expression of MRP8 and MRP14 in Human Dendritic Cells
Kumar, A. V., Steinkasserer, A., & Berchtold, S. (2003) · International Archives of Allergy and Immunology · doi:10.1159/000073263 · Cited by 35 · see citing works
Rampersad, R. R., Esserman, D. A., McGinnis, M. W., et al. (2009) · Scandinavian Journal of Rheumatology · doi:10.3109/03009740902895743 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Resolution of Inflammation: What Controls Its Onset?
Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638 · see citing works
Martin, O. P., Wallace, M. S., Oetheimer, C., Patel, H. B., Butler, E. C., Wong, L. P., Huang, P., Elbaz, J., Costentin, C., Salloum, S., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02255-y · Cited by 45 · see citing works
- Authors
- Averill, M. M., Barnhart, S., Becker, L., Li, X., Heinecke, J. W., LeBoeuf, R. C., Hamerman, J. A., Sorg, C., Kerkhoff, C., & Bornfeldt, K. E.
- Affiliations
- University of Washington (US)
- ORCID
- Venue
- Circulation
- Published
- 2011-03-22
- Volume
- 123
- Issue
- 11
- Pages
- 1216-1226
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3072335
- OpenAlex
- W1973778351
- Cited by
- 155
- References
- 40
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 12 · 2021: 8 · 2020: 13 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 18
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL097365, P01HL030086, P01HL092969, HL-079382, T32-HL-07828, R01HL097365, HL 092969, R01HL079382, HL030086, R01HL062887, T32HL007828, HL062887)
- National Institute of Allergy and Infectious Diseases (R01AI081948, R01AI073441, AI073441)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- S100A9, atherosclerosis, insulin resistance, neutrophils, dendritic cells, macrophages, myeloid cells, bone marrow chimeras, TLR4, cytokine production, macrophage maturation, inflammation, obesity
- MeSH terms
- Adipose Tissue, Animals, Dendritic Cells, Inflammation, Insulin Resistance, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Neutrophils, Phenotype, Receptors, LDL, Calgranulin A, Calgranulin B, Atherosclerosis, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice
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
