EFFECT OF ACTIVATION ON ADHESION OF FLOWING NEUTROPHILS TO CULTURED ENDOTHELIUM - TIME-COURSE AND INHIBITION BY A CALCIUM-CHANNEL BLOCKER (NITRENDIPINE)

1 Adhesion of neutrophils to vascular endothelium plays an important r ole in inflammation and thrombosis. Modulation of adhesion may be ther apeutic in these conditions. 2 A flow model was used to quantify adhes ion of neutrophils to human cultured umbilical vein endothelial cells. The time course of the neutrophil response to activation by N-formyl- methionyl-leucyl-phenylalanine (fMLP, 10(-7) M) was studied and the in hibitory effects of the calcium-channel blockers, nitrendipine and nif edipine, were investigated. 3 Neutrophils adhered firmly to the endoth elial cells without rolling, but initial attachment was highly depende nt on shear stress; doubling the stress from 0.05 to 0.1 Pa decreased the number of neutrophils adhering by over 80%. 4 Adhesion rapidly inc reased after activation of neutrophils by fMLP, peaking at 1-3 min pos ttreatment, and then decreased over the next 10-12 min. A monoclonal a ntibody to the beta2-integrin component CD18 inhibited adhesion by ove r 80% for activated or unactivated cells. 5 The Ca-channel blocker, ni trendipine, but not nifedipine, significantly inhibited the fMLP-induc ed increase of adhesion in a dose-dependent manner (10(-8) to 10(-6) m ). Dihydropyridines may be useful agents for modifying neutrophil func tion.