Integrin-Mediated Inhibition Of Interleukin-8 Secretion From Human Neutrophils By Collagen Type I

The function of neutrophils in the inflammatory response is modulated by contact with ECM proteins. We have now investigated the effect of collagen type I on secretion of the cytokine IL-8 by human neutrophils in vitro. Collagen type I inhibited the secretion of IL-8 from neutrophils maintained under basal conditions or stimulated with fMLF. This effect was accompanied by down-regulation of IL-8 mRNA, and it appeared to be specific to collagen type I among ECM proteins, in that it was not observed with fibronectin or laminin. The inhibitory effect of collagen type I on IL-8 secretion was dependent on collagen concentration and cell density. It was also abolished in the presence of antibodies to integrin alpha 2 beta 1 but was not affected by antibodies to integrin alpha 5 beta 1 or beta 4. Our results thus suggest that collagen type I inhibits the secretion of IL-8 by human neutrophils in a selective manner and that this effect is mediated by the interaction of collagen with integrin alpha 2 beta 1. J. Leukoc. Biol. 87: 487-491; 2010.