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.
Norsworthy
Peter J
PJ
Rheumatology Section, Division of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
Fossati-Jimack
Liliane
L
Cortes-Hernandez
Josefina
J
Taylor
Philip R
PR
Bygrave
Anne E
AE
Thompson
Richard D
RD
Nourshargh
Sussan
S
Walport
Mark J
MJ
Botto
Marina
M
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