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

• Published in: European journal of immunology 2008-05, Vol.38 (5), p.1414-1422
• Main Authors: Tron, Kyrylo, Manolov, Dimitar E, Röcker, Carlheinz, Kächele, Martin, Torzewski, Jan, Nienhaus, G. Ulrich
• Format: Article
• Language: English
• Subjects: C‐reactive protein; Immunoglobulin receptors; Ultrasensitive confocal microscopy
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200738002

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 FcγRI and FcγRIIa. Using ultrasensitive confocal live-cell imaging, we have studied CRP binding to FcγR 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 FcγRI and FcγRII. They were shown to bind fluorescently labeled CRP with micromolar affinity, KD = (6.6 ± 1.5) μM. CRP binding could be inhibited by pre-incubation with human but not mouse IgG and was thus FcγR-specific. Blocking of FcγRI by an FcγRI-specific antibody abolished CRP binding essentially completely, whereas application of antibodies against FcγRII 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 FcγRI, but not FcγRII. These results provide clear evidence of specific interactions between CRP and FcγR (predominantly FcγRI) naturally expressed on macrophage-like cells.