CRP Promotes Monocyte‐Endothelial Cell Adhesion via Upregulation of CD32 and CD64 and NFKb activity in Human Aortic Endothelial Cells under Static and Flow Conditions

Monocyte‐endothelial cell adhesion (MEA) is a key early event in atherogenesis. CRP, a cardiovascular risk marker, appears to be pro‐atherogenic. CRP stimulates intercellular and vascular cell adhesion molecules (ICAM, VCAM) in human aortic endothelial cells (HAEC) and induces MEA. Thus, in this study, we examined the mechanisms by which CRP promotes MEA in HAEC under static conditions and tested the effect of CRP on adhesion under shear flow. CRP was purified from human ascites/pleural fluid (azide‐free, endotoxin < 1EU/mg). Incubation of HAEC for 8h with CRP (>25ug/mL) upregulated NFKb activity and this correlated with a significant increase in ICAM (54% increase, p<0.001), VCAM (41% increase, p<0.01) and MEA (44% increase, p<0.02) compared to control. Pre‐incubation with antibodies to CD32 and CD64 but not CD16 effectively inhibited this activation. Blocking NFKb activity with inhibitors/dominant negative Ikappa B significantly decreased ICAM, VCAM and subsequent monocyte‐endothelial cell MEA. Pre‐incubation with antibodies to CD32 and CD64 resulted in attenuation of CRP‐induced NFkb activity, ICAM, VCAM and MEA under static conditions. Furthermore, CRP activated MEA significantly in shear flow (2 dynes/cm2) (p=0.002). Thus, in HAEC, CRP upregulates monocyte‐endothelial rolling and firm adhesion via upregulation of NFKb and this can be inhibited by blocking the Fc gamma receptors, CD32 and CD64.