Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death receptor

Apoptosis and clearance of neutrophils is essential for successful resoluti on of inflammation, Altered signaling via the Fas receptor could explain th e observed prolongation of neutrophil lifespan and associated tissue injury at inflammatory sites, We therefore compared inflammatory neutrophils extr acted from joints of rheumatoid arthritis patients, with peripheral blood n eutrophils, Inflammatory neutrophils underwent constitutive apoptosis in cu lture more rapidly than peripheral blood neutrophils; this was not explaine d by changes in surface expression of Fas or by induction of Fas ligand. In flammatory neutrophils remained sensitive to Fas-induced death, at levels c omparable to those seen in peripheral blood neutrophils. Similarly, granulo cyte-macrophage colony-stimulating factor reduced apoptosis but did not abo lish signaling via Fas, These data provide evidence for the rate of apoptos is in inflammatory neutrophils being continually modulated by death and sur vival signals in the inflammatory milieu. This allows for rapid resolution of inflammation as levels of survival factors fall, and suggests new strate gies for inducing resolution of inflammation.