C-reactive protein specifically binds to Fcγ receptor type I on a macrophage-like cell line

Abstract

C-reactive protein (CRP) is a prototype acute-phase protein that may be intimately involved in human disease. Its cellular receptors are still under debate; the main candidates are FcR for immunoglobulin G, as CRP was shown to bind specifically to FcyRI and FcλRIIa. Using ultrasensitive confocal live-cell imaging, we have studied CRP binding to FcλR naturally expressed in the plasma membranes of cells from a human leukemia cell line (Mono Mac 6). These macrophage-like cells express high levels of FcλRI and FcλRII. They were shown to bind fluorescently labeled CRP with micromolar affinity, KD = (6.6 ± 1.5) pM. CRP binding could be inhibited by pre-incubation with human but not mouse IgG and was thus FcλR-specific. Blocking of FcλRI by an PcλRI-specific antibody abolished CRP binding essentially completely, whereas application, of antibodies against FcλRII did not have a noticeable effect. In fluorescence images of Mono Mac 6 cells, the intensity patterns of bound CRP were correlated with those of FcλRI, but not FcλRII. These results provide clear evidence of specific interactions between CRP and FcλR (predominantly FcλRI) naturally expressed on macrophage-like cells. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.