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© The Rockefeller University Press, 0021-9525/1999//767 $5.00
The Journal of Cell Biology, Volume 144, Number 4, , 1999 767-775

Regular Articles

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



P. Hermann*, M. Armant*,{ddagger}, E. Brown||, M. Rubio*, H. Ishihara*, D. Ulrich§, R.G. Caspary§, F.P. Lindberg||, R. Armitage§, C. Maliszewski§, G. Delespesse*, and M. Sarfati*

* Laboratoire Allergie, Centre de recherché Louis-Charles Simard, Pavillon Notre-Dame, Centre Hospitalier Université de Montréal (CHUM), Montreal, Quebec H2L 4M1, Canada; {ddagger} Laboratory for Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892; § Immunex Research Development Corporation, Seattle, Washington 98101; and || Division of Infectious Diseases, Washington University, St. Louis, Missouri 63110

The vitronectin receptor, {alpha}vβ3 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-{alpha}, IL-12, and IFN-{gamma} release). Surprisingly, anti-CD47 and β3 mAbs do not block sCD23 binding to {alpha}v+β3+ 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+β3+/CD47– cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified {alpha}v protein 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 for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Key Words: CD47 • CD23 • vitronectin receptor • TNF-{alpha} • IFN-{gamma}

Abbreviations used in this paper: B, biotinylated; Fn, fibronectin; sCD23, soluble CD23; TSP, thrombospondin; Vn, vitronectin; VnR, vitronectin receptor.

P. Hermann and M. Armant contributed equally to this study.


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