Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima without affecting endothelium-dependent relaxation. Role of P-selectin.
Inflammatory cell deposition in atherosclerotic blood vessels has been thought to relate to loss of endothelium-derived nitric oxide (NO). To examine whether cell deposition correlates temporally with the loss of NO activity, rat aortic rings were incubated with buffer, native LDL (n-LDL), oxidized LDL (ox-LDL), or the endothelium-derived relaxing factor synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) for 2 hours, and vascular contractile response to norepinephrine and relaxant response to acetylcholine, thrombin, and calcium ionophore A23,187 were examined. Thereafter, the rings were exposed to biotin-fluorescein isothiocyanate-labeled fluorescent or unlabeled leukocytes for 30 minutes. Cell adhesion was quantitated by fluorescent microscopy as well as by scanning electron microscopy. Incubation with n-LDL or ox-LDL did not affect either the contractile or the relaxant response of rings. However, leukocyte adhesion increased markedly in all ox-LDL-treated rings but not in those treated with n-LDL. Thus, leukocyte adhesion occurred independent of NO activity. In keeping with this concept, pretreatment of rings with the NO precursor L-arginine failed to influence leukocyte adhesion to rings incubated with ox-LDL. Treatment of rings with L-NAME also resulted in adhesion of a large number of leukocytes. Furthermore, all rings treated with ox-LDL or L-NAME demonstrated marked expression of P-selectin leukocyte adhesion molecules, determined by immunohistochemistry. Pretreatment of rings with the P-selectin blocking antibody PB1.3 markedly decreased deposition of leukocytes in rings exposed to ox-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Mehta
A
A
Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.
Yang
B
B
Khan
S
S
Hendricks
J B
JB
Stephen
C
C
Mehta
J L
JL
D000818:Animals; D001011:Aorta / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010084:Oxidation-Reduction; D019007:P-Selectin / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D008077:Lipoproteins, LDL; D019007:P-Selectin