The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23

The vitronectin receptor, alpha(v)beta(3) integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitro nectin (Vn) is not a ligand of CD47, anti-CD47 and beta(3) mAbs suppress Vn , but not fibronectin (Fn) binding and function. Here, we show that anti-CD 47, anti-beta(3) mAb and Vn, but not Fn, inhibit sCD23-mediated proinflamma tory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti -CD47 and beta(3) mAbs do not block sCD23 binding to alpha(v)(+)beta(3)(+) T cell lines, whereas Vn and an alpha(v) mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alpha(v)(+)beta(3)(+)/CD47(-) cell lines, but coexpre ssion of CD47 increases binding. Moreover, sCD23 binds purified alpha(v) pr otein and a single human alpha(v) chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor f or sCD23 to mediate its proinflammatory activity and, as such, may be invol ved in the inflammatory process of the immune response.