C-reactive protein promotes monocyte-platelet aggregation: an additional link to the inflammatory-thrombotic intricacy.
BACKGROUND
C-reactive protein (CRP) is a risk marker for cardiovascular events in humans with pro-thrombotic activities in men and mice. Formation of monocyte-platelet aggregates (MPAs) in the blood correlates with acute cardiovascular disease and provides a possible inflammatory-thrombotic link. We investigated the effect of CRP on MPA ex vivo and in vivo.


RESULTS
Monocyte-platelet aggregation was examined by flow cytometry with dual-labeling for monocytes and platelets. Incubation of human blood with rhCRP doubled MPA formation. CRP-induced MPA formation is calcium and P-selectin dependent. Blocking antibodies to the Fc gamma receptor II had no significant effect on MPA formation. Similar effects were noted in transgenic mice, which express the human CRP gene (CRPtg). Constitutive monocyte counts and MPA levels were similar in wild-type and CRPtg mice. Lipopolysaccharide injection more than fourfold increased monocyte levels in wildtype and CRPtg mice, and preferentially increased MPA in CRPtg compared with wildtype mice.


CONCLUSIONS
CRP promotes MPAtion ex vivo and in vivo. CRP-induced aggregation is calcium-dependent and mediated via P-selectin glycoprotein ligand-1 binding. Our results suggest an inflammatory-thrombotic link that is regulated by high levels of CRP. This relationship provides a potential mechanism for CRP's thrombogenic effects and a potential therapeutic target for future intervention.
Danenberg
Haim D
HD
Heart Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel. danen@md.huji.ac.il
Kantak
Neelesh
N
Grad
Etty
E
Swaminathan
Rajesh V
RV
Lotan
Chaim
C
Edelman
Elazer R
ER
D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*
D002097:C-Reactive Protein; D002118:Calcium