Untersuchungen zur Interaktion von C-reaktivem Protein mit Immunglobulinrezeptoren auf monozytären Zellen und möglichen Liganden in atherosklerotischen Läsionen
Kächele, Martin Felix
LicenseStandard (Fassung vom 01.10.2008)
C-reactive protein (CRP), the prototype of human acute-phase protein, is considered to be a potent cardiovascular risk marker. However, its active involvement in cardiovascular disease is being controversially discussed. Fc-receptors (FcR) for human immunoglobulin G seem to be the main candidates for binding to cells; a specific CRP binding has been shown for Fc-gamma-RI and Fc-gamma-RIIa. Previous works on CRP showed inconsistent results for a CRP binding to low-density lipoprotein (LDL), a key-player in cardiovascular disease. By using ultrasensitive confocal fluorescence live-cell imaging, this work wanted to show 1) whether CRP binds also to Fc-gamma-RIII, 2) which receptor is the most important one for CRP binding to macrophage-like cells and 3) if there is any interaction between CRP and LDL. METHODS: For Fc-gamma-RIII binding studies, overexpressing receptor-transfected, COS-7 cells were used; as a model for macrophages, this work compares the cell lines Mono Mac 6 and U-937. RESULTS: 1) Incubation of transfected cells with fluorescently labeled CRP showed no binding to Fc-gamma RIII. 2) Alternating inhibition of FcR by IgG and specific antibodies turned out Fc-gamma RI to be the most important receptor for CRP binding on macrophage-like cells. 3) By fluorescence correlation spectroscopy, a moderate binding of native LDL to CRP could be observed in solution. This complex seems to enhance CRP binding to cells; yet, the nature of this interaction has to be further elucidated. CONCLUSION: These results show a growing evidence for an active involvement of CRP in cardiovascular disease. Further studies should be undertaken with primary cells and proper animal models in order to confirm these findings.
Subject HeadingsArteriosklerose [GND]
C-reaktives Protein [GND]
C-reactive protein [MeSH]