Activated polymorphonuclear leukocytes induce constriction of canine coronary artery via Mac-1, but not LFA-1, and ICAM-1

Polymorphonuclear leukocytes (PMNs) can induce endothelium-dependent constriction of the vascular ring. We evaluated the roles of adhesion molecules in PMNs-induced coronary vasoconstriction. We measured changes in the isometric tension of isolated rings of canine coronary arteries with and without endothelium suspended in an organ chamber after the addition of autologous PMNs. In concentration of 5 x 10(5) to 1 x 10(7) cells/ml, fMLP-stimulated PMNs increased the tension of coronary artery with endothelium in a dose-dependent manner (23+/-3 to 102+/-11% of KCl-induced constriction). PMNs did not damage the endothelial function of coronary arteries as determined by an acetylcholine exposure, Mechanical rubbing of the endothelial cells abolished the PMN-induced vasoconstriction. The PMN-induced vasoconstriction (5 x 10(6) cells/ml: 98+/-8% of KCl-induced constriction) was inhibited when PMNs were pretreated with the monoclonal antibody against Mac-1 (54+/-4% of KCl-induced constriction) but not against LFA-1 (94+/-5% of KCl-induced constriction) and when endothelial cells were pretreated with the monoclonal antibody against ICAM-1 (31+/-2% of KCl-induced constriction). The PMN-induced vasoconstriction was inhibited when PMNs were pretreated with the monoclonal antibody against CD18, and the extent of inhibition was comparable with CD11b/CD18, The combination of pretreatments of PMNs with CD11b/CD18 and of endothelium with ICAM-1 did not inhibit the vasoconstriction more than ICAM-1 alone. These results suggest that activated PMNs may mediate adherent-dependent constriction of canine coronary artery via Mac-1 (CD11b/CD18), but not LFA-1 (CD11a/CD18), with ICAM-1. (C) 1996 Academic Press Limited.