The Vitronectin Receptor and its Associated CD47 Molecule Mediates Proinflammatory Cytokine Synthesis in Human Monocytes by Interaction with Soluble CD23

Abstract

The vitronectin receptor, αvβ3 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 vitronectin (Vn) is not a ligand of CD47, anti-CD47 and β3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-β3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-α, IL-12, and IFN-γ release). Surprisingly, anti-CD47 and β3 mAbs do not block sCD23 binding to αv+β3+ T cell lines, whereas Vn and an αv mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds αv+β3+/CD47− cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified αv protein and a single human αv chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.