Nitric oxide regulates interactions of PMN with human brain microvessel endothelial cells.
The hypothesis that the NO/cGMP pathway modulates PMN adhesion to human brain microvessel endothelial cells (HBMEC) was examined. Human PMN were incubated with resting or TNF-alpha-treated endothelial monolayers, and adhesion was quantified by light microscopy. TNF-alpha upregulated PMN adhesion in a time-dependent manner. Treatment of HBMEC with the NO donors SNP and DETA NONOate for 4 or 24 h decreased PMN adhesion. This was completely reversed by the guanylyl cyclase inhibitor ODQ, while addition of a cGMP agonist (8-Br-cGMP) decreased PMN adhesion. NO donors did not affect the levels of E-selectin or ICAM-1 in HBMEC. However, pre-treatment of PMN with NO donors or 8-Br-cGMP decreased their adhesion to recombinant E-selectin and ICAM-1, suggesting an effect of NO on PMN. These findings indicate that NO modulates PMN-HBMEC interactions through cGMP and decreases the binding of PMN to the adhesion molecules E-selectin and ICAM-1.
Wong
Donald
D
Department of Psychiatry and The Brain Research Centre, Section of Neuropathology, Vancouver Hospital, The University of British Columbia, Vancouver, BC, Canada.
Prameya
Rukmini
R
Dorovini-Zis
Katerina
K
Vincent
Steven R
SR
D015153:Blotting, Western; D001921:Brain / Q000098:blood supply*; D002448:Cell Adhesion; D002478:Cells, Cultured; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008833:Microcirculation; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D019040:E-Selectin; D009603:Nitroso Compounds; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases