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Journal of Dental Research
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Biological

S100A8 Triggers Oxidation-sensitive Repulsion of Neutrophils

H.Y. Sroussi1,*, J. Berline2, P. Dazin3, P. Green4 and J.M. Palefsky2

1 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;
2 Department of Medicine,
3 Howard Hughes Medical Institute, and
4 Department of Oral and Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA, USA

Correspondence: * corresponding author, sroussih{at}uic.edu

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).

Key Words: S100A8 • anti-inflammatory • fugetaxis • oxidation • neutrophil

Journal of Dental Research, Vol. 85, No. 9, 829-833 (2006)
DOI: 10.1177/154405910608500910
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