Deficiency of decay-accelerating factor and complement receptor 1-related gene/protein y on murine platelets leads to complement-dependent clearance by the macrophage phagocytic receptor CRIg.
Complement activation on human platelets is known to cause platelet degranulation and activation. To evaluate how normal platelets escape complement attack in vivo, we studied the fate of murine platelets deficient in 2 membrane complement regulatory proteins using an adoptive transfer model. We show here that deficiency of either decay-accelerating factor (DAF) or complement receptor 1-related gene/protein y (Crry) on murine platelets was inconsequential, whereas DAF and Crry double deficiency led to rapid clearance of platelets from circulation in a complement- and macrophage-dependent manner. This finding contrasted with the observation on erythrocytes, where Crry deficiency alone resulted in complement susceptibility. Quantitative flow cytometry showed DAF and Crry were expressed at similar levels on platelets, whereas Crry expression was 3 times higher than DAF on erythrocytes. Antibody blocking or gene ablation of the newly identified complement receptor CRIg, but not complement receptor 3 (CR3), rescued DAF/Crry-deficient platelets from complement-dependent elimination. Surprisingly, deficiency of CRIg, CR3, and other known complement receptors failed to prevent Crry-deficient erythrocytes from complement-mediated clearance. These results show a critical but redundant role of DAF and Crry in platelet survival and suggest that complement-opsonized platelets and erythrocytes engage different complement receptors on tissue macrophages in vivo.
Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
David D
DD
Kim
Takashi
T
Miwa
Yuko
Y
Kimura
Reto A
RA
Schwendener
Menno
M
van Lookeren Campagne
Wen-Chao
WC
Song
D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D018958:CD55 Antigens / Q000502:physiology*; D002470:Cell Survival; D003167:Complement Activation; D003165:Complement System Proteins; D004912:Erythrocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b
D018958:CD55 Antigens; C081470:Cr1l protein, mouse; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C509992:VSIG4 protein, mouse; D003165:Complement System Proteins