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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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Submitted April 11, 2005
Accepted October 30, 2005
Species- and cell-type specific interactions between CD47 and human SIRP
Shyamsundar Subramanian, Ranganath Parthasarathy, Shamik Sen, Eric T Boder, and Dennis E Discher*
School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA
* Corresponding author; email: discher{at}seas.upenn.edu.
CD47 on red blood cells (RBC) reportedly signals "self" by binding SIRP on phagocytes - at least in mice [Oldenborg et al, Science 2000]. 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 as a probe, antibody-inhibitable binding to CD47 was found only with human and pig RBC (not mouse, rat, or cow). In addition, CD47-mediated adhesion of human and pig RBC to SIRP-surfaces resists sustained forces in centrifugation (as confirmed by atomic force microscopy), but only at SIRP coating densities far above those measurable on human neutrophils, monocytes, and THP-1 macrophages. While interactions strengthen with deglycosylation of SIRP, low copy numbers explain the absence of RBC adhesion to phagocytes under physiological 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, bone-marrow derived mesenchymal stem cells were assayed and found to display CD47 but not bind SIRP significantly. The results thus demonstrate that SIRP-CD47 interactions, which reportedly define "self", exhibit cell-type specificity and limited cross-species reactivity.
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