Species- and cell type-specific interactions between CD47 and human SIRPalpha.
CD47 on red blood cells (RBCs) reportedly signals "self" by binding SIRPalpha 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 SIRPalpha1 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 SIRPalpha1 surfaces resists sustained forces in centrifugation (as confirmed by atomic force microscopy) but only at SIRPalpha-coating densities far above those measurable on human neutrophils, monocytes, and THP-1 macrophages. While interactions strengthen with deglycosylation of SIRPalpha1, 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 SIRPalpha1, bone marrow-derived mesenchymal stem cells were assayed and found to display CD47 but not bind SIRPalpha1 significantly. The results thus demonstrate that SIRPalpha-CD47 interactions, which reportedly define self, exhibit cell type specificity and limited cross-species reactivity.
Subramanian
Shyamsundar
S
School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
Parthasarathy
Ranganath
R
Sen
Shamik
S
Boder
Eric T
ET
Discher
Dennis E
DE
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001773:Blood Cells; D051928:CD47 Antigen / Q000032:analysis / Q000378:metabolism*; D002448:Cell Adhesion; D003429:Cross Reactions; D004912:Erythrocytes; D006031:Glycosylation; D006801:Humans; D059630:Mesenchymal Stem Cells; D010586:Phagocytes; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D017634:Self Tolerance; D013045:Species Specificity; D013552:Swine; D014018:Tissue Distribution
D000943:Antigens, Differentiation; D051928:CD47 Antigen; D011971:Receptors, Immunologic; C501920:SIRPA protein, human