Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock
Abstract
To identify new components that regulate the inflammatory cascade during sepsis, we characterized the functions of myeloid-related protein-8 (Mrp8, S100A8) and myeloid-related protein-14 (Mrp14, S100A9), two abundant cytoplasmic proteins of phagocytes. We now demonstrate that mice lacking Mrp8-Mrp14 complexes are protected from endotoxin-induced lethal shock and Escherichia coli-induced abdominal sepsis. Both proteins are released during activation of phagocytes, and Mrp8-Mrp14 complexes amplify the endotoxin-triggered inflammatory responses of phagocytes. Mrp8 is the active component that induces intracellular translocation of myeloid differentiation primary response protein 88 and activation of interleukin-1 receptor-associated kinase-1 and nuclear factor-kappaB, resulting in elevated expression of tumor necrosis factor-alpha (TNF-alpha). Using phagocytes expressing a nonfunctional Toll-like receptor 4 (TLR4), HEK293 cells transfected with TLR4, CD14 and MD2, and by surface plasmon resonance studies in vitro, we demonstrate that Mrp8 specifically interacts with the TLR4-MD2 complex, thus representing an endogenous ligand of TLR4. Therefore Mrp8-Mrp14 complexes are new inflammatory components that amplify phagocyte activation during sepsis upstream of TNFalpha-dependent effects.
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S100A8/9 bind to TLR4 and RAGE, which activate diverse signaling cascades.
“S100A8/9 bind to Toll-like receptor 4 (TLR4) and RAGE (receptor for advanced glycation end products), which activate diverse signaling cascades (Gebhardt et al., 2006; Vogl et al., 2007).”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Vogl et al., 2007
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“Once released from the cell, calprotectins function as an endogenous agonist to bind TLR4 (S100A8/A9 and S100A12) (26) and RAGE (S100A8/A9 and S100A7) [(6, 31, 71) #3535].”
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Pattanaik, D., Brown, M. A., Postlethwaite, B. C., & Postlethwaite, A. E. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00272 · Cited by 423 · see citing works
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Damo, S. M., Kehl-Fie, T. E., Sugitani, N., Holt, M. E., Rathi, S., Murphy, W. J., Zhang, Y., Betz, C., Hench, L., Fritz, G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220341110 · Cited by 388 · see citing works
“In addition to having direct antimicrobial properties, CP is a known activator of the cell-surface receptors toll-like receptor 4 and receptor for advanced glycation end products and acts as a chemoattractant for macrophages (38, 39).”
BackgroundBiomarkers in acute kidney injury – pathophysiological basis and clinical performance
Schrezenmeier, E. V., Barasch, J. M., Budde, K., Westhoff, T. H., & Schmidt-Ott, K. M. (2016) · Acta Physiologica · doi:10.1111/apha.12764 · Cited by 414 · see citing works
“2009), but it has been shown that S100A8 and S100A9 are endogenous activators of toll-like receptor 4 (Vogl et al. 2007) (Fig.”
BackgroundRAGE signaling sustains inflammation and promotes tumor development
Gebhardt, C., Riehl, A., Durchdewald, M., Németh, J., Fürstenberger, G., Müller‐Decker, K., Enk, A., Arnold, B., Bierhaus, A., Nawroth, P. P., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20070679 · Cited by 380 · see citing works
β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares
Goldberg, E. L., Asher, J. L., Molony, R. D., Shaw, A. C., Zeiss, C. J., Wang, C., Morozova-Roche, L. A., Herzog, R. I., Iwasaki, A., & Dixit, V. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.004 · Cited by 370 · see citing works
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“These proteins stimulate matrix metalloproteinase (MMP) production in macrophages (30) and chondrocytes (29) via TLR-4 signaling.”
BackgroundExercise-Induced Splanchnic Hypoperfusion Results in Gut Dysfunction in Healthy Men
van Wijck, K., Lenaerts, K., van Loon, L. J. C., Peters, W. H. M., Buurman, W. A., & Dejong, C. H. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022366 · Cited by 359 · see citing works
“MPO plays a role in oxidative processes, while calprotectin and one of its constituents, myeloid-related protein-8 (Mrp8, S100A8), are identified as strong activators of the innate Toll-like receptor 4 signaling pathway, resulting in the expression of pro-inflammatory cytokines [30].”
BackgroundRole of S100 proteins in health and disease
Gonzalez, L. L., Garrie, K., & Turner, M. D. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118677 · Cited by 363 · see citing works
Islet inflammation in type 2 diabetes and physiology
Eguchi, K., & Nagai, R. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88877 · Cited by 359 · see citing works
Björk, P., Björk, A., Vogl, T., Stenström, M., Liberg, D., OLSSON, A. G., Roth, J., Ivars, F., & Leanderson, T. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000097 · Cited by 357 · see citing works
Self-citationThe NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype
Basiorka, A. A., McGraw, K. L., Eksioglu, E. A., Chen, X., Johnson, J., Zhang, L., Zhang, Q., Irvine, B. A., Cluzeau, T., Sallman, D. A., et al. (2016) · Blood · doi:10.1182/blood-2016-07-730556 · Cited by 356 · see citing works
S100A8/A9 activate key genes and pathways in colon tumor progression
Ichikawa, M., Williams, R., Wang, L., Vogl, T., & Srikrishna, G. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0394 · Cited by 346 · see citing works
Self-citationInflammation-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
Liu, J. Z., Jellbauer, S., Poe, A. J., Ton, V., Pesciaroli, M., Kehl-Fie, T. E., Restrepo, N. A., Hosking, M. P., Edwards, R. A., Battistoni, A., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.017 · Cited by 328 · see citing works
Self-citationZambetti, N. A., Ping, Z., Chen, S., Kenswil, K. J. G., Mylona, M. A., Sanders, M. A., Hoogenboezem, R. M., Bindels, E. M. J., Adisty, M. N., Van Strien, P. M. H., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.08.021 · Cited by 342 · see citing works
Cigarette Smoke-Induced Pulmonary Inflammation Is TLR4/MyD88 and IL-1R1/MyD88 Signaling Dependent
Doz, E., Noulin, N., Boichot, E., Guénon, I., Fick, L., Bert, M. L., Lagente, V., Ryffel, B., Schnyder, B., Quesniaux, V. F. J., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.2.1169 · Cited by 334 · see citing works
Nie, X., Kitaoka, S., Tanaka, K., Segi‐Nishida, E., Imoto, Y., Ogawa, A., Nakano, F., Tomohiro, A., Nakayama, K., Taniguchi, M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.035 · Cited by 318 · see citing works
“Among these genes, S100a8 and S100a9, which were upregulated in both susceptible and resilient mice, have been shown to form a heterodimer, and, as ligands, to be functionally related to TLR4 and, possibly, TLR2 (Coveney et al., 2015; Vogl et al., 2007).”
Induction of myelodysplasia by myeloid-derived suppressor cells
Chen, X., Eksioglu, E. A., Zhou, J., Zhang, L., Djeu, J., Fortenbery, N., Epling-Burnette, P., Van Bijnen, S., Dolstra, H., Cannon, J., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67580 · Cited by 316 · see citing works
“Given our findings that S100A9 triggers CD33/Siglec 3 signaling and is involved in MDSC activation (17, 18, 37), we generated S100A9Tg mice to study MDSC-associated inflammation (37).”
In vivo regulation of interleukin 1β in patients with cryopyrin-associated periodic syndromes
Lachmann, H. J., Lowe, P. J., Felix, S. D., Rordorf, C. M., Leslie, K. S., Madhoo, S., Wittkowski, H., Bek, S., Hartmann, N., Bosset, S., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082481 · Cited by 313 · see citing works
Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis
Guo, J., & Friedman, S. L. (2010) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-3-21 · Cited by 311 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
“1 F), in agreement with studies of activation-associated S100a8 and S100a9 expression in peripheral immune cells (Vogl et al., 2007; Austermann et al., 2014).”
ResultLoser, K., Vogl, T., Voskort, M., Lueken, A., Kupas, V., Nacken, W. K. F., Klenner, L., Kuhn, A., Foell, D., Sorokin, L. M., et al. (2010) · Nature Medicine · doi:10.1038/nm.2150 · Cited by 296 · see citing works
Self-citationRAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis
Turovskaya, O., Foell, D., Sinha, P., Vogl, T., Newlin, R., Nayak, J., Nguyen, M. T. X., Olsson, A., Nawroth, P. P., Bierhaus, A., et al. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn188 · Cited by 296 · see citing works
Self-citationFoell, D. (2010) · JAMA · doi:10.1001/jama.2010.375 · Cited by 291 · see citing works
Self-citationBiomarkers of acute kidney injury: the pathway from discovery to clinical adoption
KASHANI, K. B., Cheungpasitporn, W., & Ronco, C. (2017) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0973 · Cited by 294 · see citing works
“No singular receptor uses calprotectin signal transduction, but S100A8 and S100A9 have been noted to be endogenous activators of Toll-like receptor 4 [138].”
BackgroundCernak, I., Merkle, A., Koliatsos, V., Bilik, J., Luong, Q., Mahota, T. M., Xu, L.-Y., Slack, N., Windle, D., & Ahmed, F. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.10.025 · Cited by 305 · see citing works
RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts
Ramasamy, R., Yan, S. F., & Schmidt, A. M. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0409230 · Cited by 283 · see citing works
Rodrı́guez, A., Ezquerro, S., Méndez-Giménez, L., Becerril, S., & Frühbeck, G. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00297.2015 · Cited by 281 · see citing works
Srikrishna, G., & Freeze, H. H. (2009) · Neoplasia · doi:10.1593/neo.09284 · Cited by 274 · see citing works
Toll-Like Receptor Signaling and Its Inducible Proteins
Satoh, T., & Akira, S. (2016) · Microbiology spectrum · doi:10.1128/microbiolspec.mchd-0040-2016 · Cited by 251 · see citing works
“In addition to LPS and other bacterial ligands, TLR4 also recognizes S100a8, a ligand derived from dying cells (6, 7).”
BackgroundKumar, V. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107087 · Cited by 276 · see citing works
Șchiopu, A., & Cotoi, O. S. (2013) · Mediators of Inflammation · doi:10.1155/2013/828354 · Cited by 269 · see citing works
“However, other authors propose S100A8 to be the main active component of the S100A8/A9 complex [40], so this issue remains controversial.”
BackgroundThe central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes
Sallman, D. A., & List, A. (2019) · Blood · doi:10.1182/blood-2018-10-844654 · Cited by 273 · see citing works
Simard, J.-C., Césaro, A., Chapeton-Montes, J. A., Tardif, M. R., Antoine, F., Girard, D., & Tessier, P. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072138 · Cited by 263 · see citing works
“S100A8 and S100A9 are presumed to bind to the PRRs, TLR4, and RAGE, thereby leading to transcription of pro-inflammatory genes [8,9].”
BackgroundS100A8 and S100A9: New Insights into Their Roles in Malignancy
Srikrishna, G. (2011) · Journal of Innate Immunity · doi:10.1159/000330095 · Cited by 260 · see citing works
RAGE and TLRs: Relatives, friends or neighbours?
Ibrahim, Z. A., Armour, C. L., Phipps, S., & Sukkar, M. B. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.07.008 · Cited by 255 · see citing works
S100A8/A9 Proteins Mediate Neutrophilic Inflammation and Lung Pathology during Tuberculosis
Gopal, R., Monin, L., Torres‐García, D., Slight-Webb, S. R., Mehra, S., McKenna, K. C., Junecko, B. A. F., Reinhart, T. A., Kolls, J. K., Báez-Saldaña, R., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201304-0803oc · Cited by 256 · see citing works
“S100A8/A9 protein levels were measured in mouse lung homogenates and culture supernatants (15) and in human serum (16) by ELISA as described before.”
BackgroundMethodSelf-citationPathophysiology of Acute Coronary Syndrome
Santos‐Gallego, C. G., Picatoste, B., & Badimón, J. J. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0401-9 · Cited by 254 · 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
Szczepański, M. J., Czystowska, M., Szajnik, M. E., Harasymczuk, M., Boyiadzis, M. M., Zagajewska, A. K. , Szyfter, W., Zeromski, J., & Whiteside, T. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3838 · Cited by 253 · see citing works
Wang, L., Chang, E. W. Y., Wong, S. C., Ong, S., Chong, D. Q. Y., & Ling, K. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1202088 · Cited by 249 · see citing works
“receptors, such as heparan sulfate (30), TLR4 (31), and carboxylated N-glycans expressed on RAGE (32, 33), on immune cells and tumor cells.”
BackgroundGuo, Q., Zhao, Y., Li, J., Liu, J., Yang, X., Guo, X., Kuang, M., Xia, H., Zhang, Z., Cao, L., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.016 · Cited by 242 · see citing works
“S100A8/A9 is an endogenous ligand of Toll-like receptor 4 (TLR4) and can trigger multiple inflammatory pathways mediated by TLR4 (Vogl et al., 2007).”
BackgroundShichita, T., Ito, M., Morita, R., Komai, K., Noguchi, Y., Ooboshi, H., Koshida, R., Takahashi, S., Kodama, T., & Yoshimura, A. (2017) · Nature Medicine · doi:10.1038/nm.4312 · Cited by 249 · see citing works
Calprotectin (S100A8/S100A9): a key protein between inflammation and cancer
Shabani, F., Farasat, A., Mahdavi, M., & Gheibi, N. (2018) · Inflammation Research · doi:10.1007/s00011-018-1173-4 · Cited by 251 · see citing works
Nutritional immunity: S100 proteins at the host–pathogen interface
Zackular, J. P., Chazin, W. J., & Skaar, E. P. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.645085 · Cited by 235 · see citing works
“It has been demonstrated that calprotectin is an endogenous agonist of TLR4 (43).”
Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes
Gañán-Gómez, I., Wei, Y., Starczynowski, D. T., Colla, S., Yang, H., Cabrero-Calvo, M., Bohannan, Z. S., Verma, A., Steidl, U., & Garcia-Manero, G. (2015) · Leukemia · doi:10.1038/leu.2015.69 · Cited by 236 · see citing works
Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9
Schneider, R. K., Schenone, M., Ferreira, M. S. V., Kramann, R., Joyce, C. E., Hartigan, C. R., Beier, F., Brümmendorf, T. H., Germing, U., Platzbecker, U., et al. (2016) · Nature Medicine · doi:10.1038/nm.4047 · Cited by 236 · see citing works
“S100A8-S100A9 expression is induced during inflammatory processes including infection, autoimmunity, and cancer 26,36,37 .”
The role of TLRs in neutrophil activation
Prince, L. R., Whyte, M. K. B., Sabroe, I., & Parker, L. C. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.06.007 · Cited by 236 · see citing works
Trial Watch: Toll-like receptor agonists in cancer immunotherapy
Smith, M. M., García-Martínez, E., Pitter, M. R., Fucikova, J. P., Špíšek, R., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1526250 · Cited by 232 · see citing works
Necroinflammation in Kidney Disease
Mulay, S. R., Linkermann, A., & Anders, H. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015040405 · Cited by 231 · see citing works
Sakaguchi, M., Murata, H., Yamamoto, K.-I., Ono, T., Sakaguchi, Y. M., Motoyama, A., Hibino, T., Kataoka, K., & Huh, N.-H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023132 · Cited by 230 · see citing works
Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation
Vogl, T., Stratis, A., Wixler, V., Völler, T., Thurainayagam, S., Jorch, S. K., Zenker, S., Dreiling, A., Chakraborty, D., Fröhling, M., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci89867 · Cited by 226 · see citing works
Self-citationTsourouktsoglou, T.-D., Warnatsch, A., Ιωάννου, Μ., Hoving, D., Wang, Q., & Papayannopoulos, V. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107602 · Cited by 227 · see citing works
“…composed of decondensed chromatin and proteins such as the cathelicidin LL-37, S100A8, and high-mobility group protein 1 (HMGB1) that have been linked to inflammation (Lande et al., 2007, 2011; Tian et al., 2007; Ulas et al., 2017; Urban et al., 2009; Urbonaviciute et al., 2008; Vogl et al., 2007).”
BackgroundBrown, G. T., & McIntyre, T. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001623 · Cited by 223 · see citing works
S100A8 and S100A9 in Cardiovascular Biology and Disease
Averill, M. M., Kerkhoff, C., & Bornfeldt, K. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.236927 · Cited by 219 · see citing works
Shao, S., Fang, H., Dang, E., Xue, K., Zhang, J., Li, B., Qiao, H., Cao, T., Zhuang, Y., Shen, S., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00746 · Cited by 220 · see citing works
“Considering that these molecules might independently contribute to keratinocyte activation, we treated keratinocytes with NETs and compared against keratinocytes treated with recombinant S100A9, S100A8, LCN2, and HSP70 proteins.”
BackgroundInfluentialKrenkel, O., Hundertmark, J., Abdallah, A. T., Kohlhepp, M., Puengel, T., Roth, T., Branco, D. P. P., Mossanen, J. C., Luedde, T., Trautwein, C., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-318382 · Cited by 220 · see citing works
“Calprotectin can be recognised via the TLR4–MyD88 axis, 28 and the receptor for advanced glycosylation end products, thereby inducing NLRP3 inflammasome formation.”
Foell, D., Wittkowski, H., & Roth, J. (2009) · Gut · doi:10.1136/gut.2008.170019 · Cited by 217 · see citing works
Self-citationCai, Z., Sanchez, A., Shi, Z., Zhang, T., Liu, M., & Zhang, D. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-1993 · Cited by 216 · see citing works
Vogl, T., Gharibyan, A. L., & Morozova‐Roche, L. A. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13032893 · Cited by 212 · see citing works
Self-citationProinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells
Ma, L., Sun, P., Zhang, J.-C., Zhang, Q., & Yao, S.-L. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.2987 · Cited by 196 · see citing works
“Recently, S100A8/A9, as the endogenous activator of TLR4 signaling, promotes lethal endotoxin‑induced shock (6).”
Background
- Authors
- 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., & Roth, J.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Roth, Johannes
- Venue
- Nature Medicine
- Published
- 2007-09
- Volume
- 13
- Issue
- 9
- Pages
- 1042-1049
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2097599737
- Semantic Scholar
- 449f0155e324615b5e473420b069ac047b594da9
- Cited by
- 1,418
- References
- 47
- Citations by year
- 2026: 61 · 2025: 52 · 2024: 80 · 2023: 86 · 2022: 79 · 2021: 83 · 2020: 77 · 2019: 74 · 2018: 70 · 2017: 92 · 2016: 92 · 2015: 92 · 2014: 73 · 2013: 104 · 2012: 75
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- S100A8, S100A9, TLR4, endotoxic shock, sepsis, endogenous ligands, phagocyte activation, MD-2, CD14, MyD88, TRAF6, NF-κB, TNF-α, Escherichia coli, inflammation
- MeSH terms
- Animals, Cells, Cultured, Endotoxins, Flow Cytometry, Humans, Ligands, Lipopolysaccharides, Pulmonary Alveoli, Shock, Septic, Tumor Necrosis Factor-alpha, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Calgranulin A, Calgranulin B, Cell Line, Tumor, Toll-Like Receptor 4, Mice
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