The proinflammatory effect of C-reactive protein on human endothelial cells depends on the FcγRIIa genotype.
BACKGROUND
The stimulatory effects of CRP (C-reactive protein) on endothelial cells are mainly mediated via FcγRIIa. This receptor exists in two different allotypes bearing either arginine (R131) or histidine (H131) at the extracellular amino acid position 131 of the mature protein, but only FcγRIIa-R131 displays high avidity for CRP. This study investigated the role of the FcγRIIa genotype in CRP-stimulated endothelial cells.


METHODS
We tested the effects of CRP on expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the endothelial release of pro-inflammatory molecules as a function of the FcγRIIa-genotype (FcγRIIa-H/H131, FcγRIIa-H/R131, FcγRIIa-R/R131) in HUVEC (Human Umbilical Vein Endothelial Cells). HUVEC were grouped according to their FcγRIIa status by genotyping with an allele specific nested-PCR. The expression of ICAM-1, VCAM-1, and E-selectin on HUVEC was detected by flow cytometry. The release of soluble markers (sCD40L, IL-6, IL-8, MCP-1, tPA, sP-selectin, and sVCAM-1) was measured using a multiplex assay for flow cytometry.


CONCLUSIONS
CRP-stimulated expression of ICAM-1 and E-selectin was dependent on the specific FcγRIIa-genotype, with most pronounced induction in HUVEC with the FcγRIIa-R/R genotype, followed by H/R and H/H. In accordance with this finding, the supernatants of stimulated HUVEC with the R/R genotype showed significantly higher levels of tPA, MCP-1, and IL-6. Our data show that CRP stimulates the expression of adhesion molecules and the release of soluble markers by HUVEC as a function of the FcγRIIa-genotype. These findings could be relevant in the context of risk stratification in patients with cardiovascular disease.
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany. Electronic address: Dorette.Raaz@uk-erlangen.de.
Dorette
D
Raaz-Schrauder
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
Arif B
AB
Ekici
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany.
Lutz
L
Klinghammer
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany.
Christian
C
Stumpf
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany.
Stephan
S
Achenbach
Department of Rheumatology and Immunology, University Hospital Erlangen, Erlangen, Germany.
Martin
M
Herrmann
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
André
A
Reis
Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany.
Christoph D
CD
Garlichs
D002097:C-Reactive Protein / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein
C-reactive protein; Cell adhesion molecules; Coronary artery disease; Cytokines; Fcγ receptor IIa gene polymorphisms