Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble β-glucan

• Published in: Immunopharmacology 2000-01, Vol.46 (1), p.39-54
• Main Authors: Yan, Jun, Větvička, Václav, Xia, Yu, Hanikýřová, Margareta, Mayadas, Tanya N, Ross, Gordon D
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; b-glucan; Biological and medical sciences; Biological response modifier; C3-receptor; CD18 Antigens; Chromium Radioisotopes; Clearance; Complement; complement component C3; complement component C3 receptors; Erythrocytes - drug effects; Erythrocytes - metabolism; Female; Glucans - metabolism; Glucans - pharmacokinetics; Glucans - therapeutic use; Immunoglobulin M - metabolism; Immunoglobulin M - pharmacology; Immunomodulators; Iodine Radioisotopes; Kinetics; Kupffer Cells - immunology; Kupffer Cells - metabolism; Liver; Macrophage; Macrophage-1 Antigen - immunology; Macrophage-1 Antigen - metabolism; Macrophage-1 Antigen - pharmacology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Opsonin Proteins - metabolism; Opsonin Proteins - pharmacology; Organ Specificity; Pharmacology. Drug treatments; Receptors, Complement 3b - immunology; Zymosan - metabolism; Zymosan - pharmacokinetics; Zymosan - therapeutic use
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(99)00157-5

Liver macrophages (Kupffer cells) play a major role in blood clearance of both C3-opsonized immune complexes and therapeutic β-glucan polysaccharides. Human Kupffer cells express three types of C3-receptors: CR1 (C3b-receptor; CD35), CR3 (iC3b- and β-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 β-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-β-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 β-glucans.