The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/147/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 1, July 7, 1997 147-152

Brief Definitive Reports

Development of Inflammatory Angiogenesis by Local Stimulation of Fas In Vivo

Luigi Biancone*, Antonella De Martino*, Viviana Orlandi§, Pier Giulio Conaldi§, Antonio Toniolo§, and Giovanni Camussi*

From the * Chair of Nephrology and § Chair of Microbiology, Department of Clinical and Biological Sciences, University of Pavia, Varese, Italy

Fas–Fas ligand interaction is thought to be a crucial mechanism in controlling lymphocyte expansion by inducing lymphocyte apoptosis. However, Fas is also broadly expressed on nonlymphoid cells, where its function in vivo remains to be determined. In this study, we describe the development 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 containing mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalization of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected in the inflammatory infiltrate. The phenomenon was dose and time dependent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogenesis 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 angiogenesis and cell infiltration did not result from recruitment of phagocytes by apoptotic cells but rather by a stimulatory signal through Fas-engagement. These findings suggest a role for Fas–Fas ligand interaction in promoting local angiogenesis and inflammation.

Address correspondence to Giovanni Camussi, Dip. di Scienze Cliniche e Biologiche, Via L. Borri 57, 21100 Varese, Italy. Phone: 39-332-278311; Fax: 39-332-260017.


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