Murine CD93 (C1qRp) contributes to the removal of apoptotic cells in vivo but is not required for C1q-mediated enhancement of phagocytosis.
Human CD93 (known as C1qRp) has been shown to be a phagocytic receptor involved in the in vitro C1q-dependent enhancement of phagocytosis. However, binding of CD93 to C1q and its function remain controversial. In this study, we have generated CD93-deficient mice (CD93(-/-)) to investigate its biological role(s). The CD93(-/-) mice were viable and showed no gross abnormalities in their development. Thioglycolate-elicited peritoneal macrophages deficient in CD93 showed a similar enhancement in complement- and FcgammaR-dependent uptake of RBC to the wild-type macrophages when plated on C1q-coated surfaces suggesting that the lack of this receptor had no effect on these C1q-mediated events. There was no impairment in either complement- or FcgammaR-dependent phagocytic assays in vivo. By contrast, the CD93(-/-) mice had a significant phagocytic defect in the clearance of apoptotic cells in vivo (human Jurkat T cells and murine thymocytes: p=0.0006 and p=0.0079, respectively) compared with strain-matched controls. However, in vitro, the CD93(-/-) macrophages showed similar engulfment of apoptotic cells to wild-type macrophages. Furthermore, no supporting evidence for a role of CD93 as an adhesion molecule was found using intravital microscopy or analyzing peritoneal cell recruitment in response to three different inflammatory stimuli (thioglycolate, zymosan A, and IL-1beta). Thus, our findings indicate that murine CD93 is expressed on the peritoneal macrophage, especially on thioglycolate-elicited cells, but does not appear to play a key role in C1q-mediated enhancement of phagocytosis or in the intercellular adhesion events tested. However, our results suggest that it may contribute to the in vivo clearance of dying cells.
Rheumatology Section, Division of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
Peter J
PJ
Norsworthy
Liliane
L
Fossati-Jimack
Josefina
J
Cortes-Hernandez
Philip R
PR
Taylor
Anne E
AE
Bygrave
Richard D
RD
Thompson
Sussan
S
Nourshargh
Mark J
MJ
Walport
Marina
M
Botto
D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000502:physiology*; D003176:Complement C3 / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D018390:Gene Targeting; D006801:Humans; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D019169:Jurkat Cells; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009895:Opsonin Proteins / Q000097:blood / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D011951:Receptors, Complement / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017452:Receptors, IgG / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013864:Thioglycolates / Q000494:pharmacology
D000276:Adjuvants, Immunologic; C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D003176:Complement C3; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009895:Opsonin Proteins; D011951:Receptors, Complement; D017452:Receptors, IgG; D013864:Thioglycolates; C032402:complement 1q receptor; D015922:Complement C1q