C-Reactive Protein Binding to Murine Leukocytes Requires Fcg Receptors

Human C-reactive protein (CRP) is an acute phase protein that binds to receptors on human and mouse leukocytes. We have recently determined that the high and low affinity receptors for CRP on human leukocytes are FcgRIIa and FcgRI, respectively. Previous work by others suggested that CRP receptors on mouse macrophages are distinct from FcgR. We have taken advantage of the availability of mice deficient in one or more FcgR to reexamine the role of FcgR in CRP binding to mouse leukocytes. Three strains of FcgR-deficient mice were examined: g-chain-deficient mice that lack FcgRI and FcgRIII, FcgRII-deficient mice, and mice deficient in both g-chain and FcgRII that lack all FcgR. No binding of CRP was detected to leukocytes from double-deficient mice, indicating that FcgR are required for CRP binding. CRP binding to leukocytes from g-chain-deficient and FcgRII-deficient mice was reduced compared with binding to leukocytes from wild-type mice. Further analysis of CRP binding to macrophages, neutrophils, and lymphocytes provides direct evidence that FcgRIIb1, FcgRIIb2, and FcgRI are the receptors for CRP on mouse leukocytes. These findings may have important implications in understanding the physiological function of CRP. The Journal of Immunology, 2000, 164: 1514–1520.