Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes.
It has been recently shown that Fas ligand (FasL) expression on islet beta grafts results in neutrophilic infiltration and graft rejection. In this study, we show that human recombinant soluble FasL is endowed with potent chemotactic properties toward human neutrophilic polymorphonuclear leukocytes (neutrophils) at concentrations incapable of inducing cell apoptosis. Furthermore, neutrophils exposed to soluble FasL did not display detectable change of intracellular Ca2+ and did not undergo superoxide production or exocytosis of primary and secondary granules. Our results show that FasL is a potent 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 FasL-mediated graft rejection, thereby offering rational bases for controlling and modulating FasL-based immunotherapies.
Ottonello
L
L
Department of Internal Medicine, University of Genova Medical School, Italy. otto@csita.unige.it
Tortolina
G
G
Amelotti
M
M
Dallegri
F
F
D000328:Adult; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D012995:Solubility; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D002118:Calcium