Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro.
Monocyte-endothelial interactions are of fundamental importance in determining the movement of monocytes from the blood stream into the vessel wall. This study reports that two endothelium-derived factors, nitric oxide and prostacyclin, alter in vitro monocyte behavior. Nitric oxide (greater than 10(-5) M) inhibited monocyte adhesion to porcine aortic endothelial cell monolayers, whereas prostacyclin (10(-9) to 10(-5) M) had no effect. Both nitric oxide and prostacyclin inhibited monocyte chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine and induced dose-dependent increases in intracellular cyclic guanosine monophosphate and cyclic adenosine monophosphate concentrations, respectively. The cell surface expression of the CD11b/CD18 adhesion receptor, a glycoprotein complex known to mediate monocyte intracellular adhesion, was not altered by either nitric oxide or by prostacyclin. Thus, endothelium-derived nitric oxide and prostacyclin may have a physiological role in modulating monocyte-vascular wall interactions. Alterations in this system may contribute to the increased monocyte emigration from the blood stream into the vessel wall observed in atherogenesis.
Bath
P M
PM
Department of Medicine, King's College School of Medicine and Dentistry, London, U.K.
Hassall
D G
DG
Gladwin
A M
AM
Palmer
R M
RM
Martin
J F
JF
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine
D015703:Antigens, CD; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011464:Epoprostenol; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D006152:Cyclic GMP