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 role in inflammation and thrombosis. Modulation of adhesion may be therapeutic in these conditions. 2. A flow model was used to quantify adhesion of neutrophils to human cultured umbilical vein endothelial cells. The time course of the neutrophil response to activation by N-formyl-methionyl-leucylphenylalanine (fMLP, 10(-7) M) was studied and the inhibitory effects of the calcium-channel blockers, nitrendipine and nifedipine, were investigated. 3. Neutrophils adhered firmly to the endothelial cells without rolling, but initial attachment was highly dependent on shear stress; doubling the stress from 0.05 to 0.1Pa decreased the number of neutrophils adhering by over 80%. 4. Adhesion rapidly increased after activation of neutrophils by fMLP, peaking at 1-3 min post-treatment, and then decreased over the next 10-12 min. A monoclonal antibody to the beta 2-integrin component CD18 inhibited adhesion by over 80% for activated or unactivated cells. 5. The Ca-channel blocker, nitrendipine, but not nifedipine, significantly inhibited the fMLP-induced increase of adhesion in a dose-dependent manner (10(-8) to 10(-6) M). Dihydropyridines may be useful agents for modifying neutrophil function.
Perry
I
I
Department of Haematology, Medical School, University of Birmingham.
Buttrum
S M
SM
Nash
G B
GB
D000328:Adult; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology*
D015703:Antigens, CD; D018821:CD18 Antigens; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009568:Nitrendipine; D009543:Nifedipine