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 Blood, 15 March 2006, Vol. 107, No. 6, pp. 2548-2556.
Prepublished online as a Blood First Edition Paper on November 15, 2005; DOI 10.1182/blood-2005-04-1463.

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RED CELLS

Species- and cell type-specific interactions between CD47 and human SIRP{alpha}

Shyamsundar Subramanian, Ranganath Parthasarathy, Shamik Sen, Eric T. Boder, and Dennis E. Discher

From the School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA.

CD47 on red blood cells (RBCs) reportedly signals "self" by binding SIRP{alpha} on phagocytes, at least in mice. Such interactions across and within species, from mouse to human, are not yet clear and neither is the relation to cell adhesion. Using human SIRP{alpha}1 as a probe, antibody-inhibitable binding to CD47 was found only with human and pig RBCs (not mouse, rat, or cow). In addition, CD47-mediated adhesion of human and pig RBCs to SIRP{alpha}1 surfaces resists sustained forces in centrifugation (as confirmed by atomic force microscopy) but only at SIRP{alpha}-coating densities far above those measurable on human neutrophils, monocytes, and THP-1 macrophages. While interactions strengthen with deglycosylation of SIRP{alpha}1, low copy numbers explain the absence of RBC adhesion to phagocytes under physiologic conditions and imply that the interaction being studied is not responsible for red cell clearance in humans. Evidence of clustering nonetheless suggests mechanisms of avidity enhancement. Finally, using the same CD47 antibodies and soluble SIRP{alpha}1, bone marrow-derived mesenchymal stem cells were assayed and found to display CD47 but not bind SIRP{alpha}1 significantly. The results thus demonstrate that SIRP{alpha}-CD47 interactions, which reportedly define self, exhibit cell type specificity and limited cross-species reactivity. (Blood. 2006;107:2548-2556)


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