DEVELOPMENT OF INFLAMMATORY ANGIOGENESIS BY LOCAL STIMULATION OF FAS IN-VIVO

Fas-Fas ligand interaction is thought to be a crucial mechanism in con trolling lymphocyte expansion by inducing lymphocyte apoptosis. Howeve r, Fas is also broadly expressed on nonlymphoid cells, where its funct ion in vivo remains to be determined. In this study, we describe the d evelopment of inflammatory angiogenesis induced by agonistic anti-Fas mAb Jo2 in a murine model where Matrigel is used as a vehicle for the delivery of mediators. The subcutaneous implants in mice of Matrigel c ontaining mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalizati on of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected i n the inflammatory infiltrate. The phenomenon was dose and time depend ent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogen esis was restricted to the agonistic anti-Fas mAb and it was absent in lpr Fas-mutant mice. Apoptotic cells were not detectable at any time inside the implant or in the surrounding tissue, suggesting that angio infiltration did not result from recruitment of phagocytes by apoptot ic cells but rather by a stimulatory signal through Fas-engagement. Th ese findings suggest a role for Fas-Fas ligand interaction in promotin g local angiogenesis and inflammation.