Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclearleukocytes

It has been recently shown that Fas ligand (FasL) expression on islet beta grafts results in neutrophilic infiltration and graft rejection. In this st udy, we show that human recombinant soluble Fast is endowed with potent che motactic properties toward human neutrophilic polymorphonuclear leukocytes (neutrophils) at concentrations incapable of inducing cell apoptosis, Furth ermore, neutrophils exposed to soluble Fast did not display detectable chan ge of intracellular Ca2+ and did not undergo superoxide production or exocy tosis of primary and secondary granules. Our results show that Fast is a po tent chemoattractant for human neutrophils without evoking their secretory responses. This finding suggests a novel proinflammatory function for this ligand and may help to clarify the mechanism governing Fast-mediated graft rejection, thereby offering rational bases for controlling and modulating F asL-based immunotherapies.