Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble beta-glucan.
Liver macrophages (Kupffer cells) play a major role in blood clearance of both C3-opsonized immune complexes and therapeutic beta-glucan polysaccharides. Human Kupffer cells express three types of C3-receptors: CR1 (C3b-receptor; CD35), CR3 (iC3b- and beta-glucan-receptor), and CR4 (iC3b-receptor; CD11c/CD18). Studies of isolated macrophages have suggested that CR3 is the major receptor mediating capture of either C3-opsonized erythrocytes (E) or beta-glucans. In this investigation, the organ distribution and function of CR3 in the clearance of IgM-opsonized E and soluble CR3-binding polysaccharides were explored in normal vs. CR3-knockout (CR3-KO) mice. Analysis of intravenously (i.v.) injected 125I-anti-CR3 showed that the major vascular reservoir of CR3 was the liver, followed by spleen and lungs. By contrast, clearance of 125I-anti-CR1 appeared to be mediated predominantly by splenic B lymphocytes, as only subsets of splenic macrophages or Kupffer cells were found to express CR1. Clearance of IgM-opsonized 51Cr-E occurred rapidly to the livers of normal mice but was nearly absent in CR3-KO mice. Soluble 125I-beta-glucan exhibited rapid clearance to the liver in normal mice, whereas clearance in CR3-KO mice was significantly reduced. In conclusion, Kupffer cell CR3 plays a crucial role in the clearance of both IgM-opsonized E and beta-glucans.
Yan
J
J
Department of Pathology, University of Louisville, KY 40292, USA.
Vetvicka
V
V
Xia
Y
Y
Hanikýrová
M
M
Mayadas
T N
TN
Ross
G D
GD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D018821:CD18 Antigens; D002860:Chromium Radioisotopes; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005936:Glucans / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009895:Opsonin Proteins / Q000378:metabolism / Q000494:pharmacology; D009928:Organ Specificity; D017463:Receptors, Complement 3b / Q000276:immunology; D015054:Zymosan / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002860:Chromium Radioisotopes; D005936:Glucans; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; D015054:Zymosan