Interactions between cells and their surroundings are important for proper function and homeostasis in a multicellular organism. These interactions can either be established between the cells and molecules in their extracellular milieu, but also involve interactions between cells. In all these situations, proteins in the plasma membranes are critically involved to relay information obtained from the exterior of the cell. The cell surface glycoprotein CD47 (integrin-associated protein (IAP)) was first identified as an important regulator of integrin function, but later also was shown to function in ways that do not necessarily involve integrins. Ligation of CD47 can induce intracellular signaling resulting in cell activation or cell death depending on the exact context. By binding to another cell surface glycoprotein, signal regulatory protein alpha (SIRPα), CD47 can regulate the function of cells in the monocyte/macrophage lineage. In this spotlight paper, several functions of CD47 will be reviewed, although some functions may be more briefly mentioned. Focus will be on the ways CD47 regulates hematopoietic cells and functions such as CD47 signaling, induction of apoptosis, and regulation of phagocytosis or cell-cell fusion. 1. Structure and Expression of CD47 in the Plasma Membrane CD47 (originally named integrin-associated protein (IAP)) is a cell surface protein of the immunoglobulin (Ig) superfamily, which is heavily glycosylated and expressed by virtually all cells in the body [1]. CD47 was first recognized as a 50？kDa protein associated and copurified with the integrin in placenta and neutrophil granulocytes and later shown to have the capacity to regulate integrin function and the responsiveness of leukocytes to RGD-containing extracellular matrix proteins [1–4]. Soon after this integrin-associated protein was cloned, it was shown to be identical to the erythrocyte cell surface antigen CD47 [5]. The fact that CD47 is also expressed by cells like erythrocytes, that do not express integrins, indicates that it can be more appropriate to refer to this protein as CD47 than using its original name integrin-associated protein (IAP). The protein is fairly well conserved between species and has about 60–70% similarity in the amino acid sequence when comparing human CD47 with that of mouse, rat, and bovine CD47. CD47 has also been shown to be identical to the OA-3/OVTL3 antigen highly expressed on most ovarian carcinomas [6, 7]. It also shows homology to a protein family of variola and vaccinia viruses [1, 5, 6], the significance of which is still unclear.
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