PMID- 16931866 OWN - NLM STAT- MEDLINE DCOM- 20070123 LR - 20190508 IS - 0022-0345 (Print) IS - 1544-0591 (Electronic) IS - 0022-0345 (Linking) VI - 85 IP - 9 DP - 2006 Sep TI - S100A8 triggers oxidation-sensitive repulsion of neutrophils. PG - 829-33 AB - The inflammatory response to tissue injury is a multi-faceted process. During this process, neutrophils migrate in the extravascular spaces, directed to the site of injury by chemical gradients generated by chemotactic molecules. S100A8, a protein associated with a wide variety of inflammatory conditions, is heavily over-expressed in association with inflammation. We hypothesized that human S100A8 possesses neutrophil-repelling properties that result in an anti-inflammatory effect in vivo. The chemotactic activity of S100A8 on neutrophils was tested in Transwell chemotaxis assays. Analysis of the data indicates that S100A8 causes a repulsion of peripheral neutrophils, an activity that S100A8 loses upon its oxidation. Using a mutant of S100A8 resistant to oxidation and consistent with the in vitro findings, we demonstrated that S100A8 causes a strong anti-inflammatory effect in the rat air-pouch model of inflammation in vivo. These data highlight a naturally occurring novel anti-inflammatory pathway and provide potential molecular targets for the development of novel anti-inflammatory therapeutics. Abbrevations: ethylene diamine tetraacetic acid (EDTA); limulus amoebocyte lysate assay (LAL); pertussis toxin (PTX); forward scatter (FSC); Interleukin-8 (IL-8); formyl-Met-Leu-Phe (fMLP); monocyte chemotactic protein 1 (MCP1). FAU - Sroussi, H Y AU - Sroussi HY AD - Department of Oral Medicine and Diagnostic Sciences, University of Illinois at Chicago, College of Dentistry (M/C 838), 801 S. Paulina St., Room 556, Chicago, IL 60612-7213, USA. sroussih@uic.edu FAU - Berline, J AU - Berline J FAU - Dazin, P AU - Dazin P FAU - Green, P AU - Green P FAU - Palefsky, J M AU - Palefsky JM LA - eng GR - P01 DE 07946/DE/NIDCR NIH HHS/United States GR - P01 DE007946/DE/NIDCR NIH HHS/United States GR - T32 DE07204/DE/NIDCR NIH HHS/United States GR - K16 DE 00386/DE/NIDCR NIH HHS/United States GR - K16 DE000386-04/DE/NIDCR NIH HHS/United States GR - T32 DE007204/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Dent Res JT - Journal of dental research JID - 0354343 RN - 0 (Calgranulin A) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - K848JZ4886 (Cysteine) RN - OF5P57N2ZX (Alanine) SB - IM MH - Alanine/metabolism MH - Animals MH - Calgranulin A/*physiology MH - Cells, Cultured MH - Chemotaxis, Leukocyte/drug effects/*physiology MH - Cysteine/metabolism MH - Flow Cytometry MH - Humans MH - Inflammation/*metabolism MH - Inflammation Mediators/*antagonists & inhibitors MH - Lipopolysaccharides MH - N-Formylmethionine Leucyl-Phenylalanine/antagonists & inhibitors MH - Neutrophils/drug effects/*physiology MH - Oxidation-Reduction MH - Rats MH - Recombinant Proteins/pharmacology PMC - PMC2248158 MID - NIHMS38060 EDAT- 2006/08/26 09:00 MHDA- 2007/01/24 09:00 PMCR- 2008/02/19 CRDT- 2006/08/26 09:00 PHST- 2006/08/26 09:00 [pubmed] PHST- 2007/01/24 09:00 [medline] PHST- 2006/08/26 09:00 [entrez] PHST- 2008/02/19 00:00 [pmc-release] AID - 85/9/829 [pii] AID - 10.1177/154405910608500910 [doi] PST - ppublish SO - J Dent Res. 2006 Sep;85(9):829-33. doi: 10.1177/154405910608500910.