© 1995 American Heart Association, Inc.
Articles |
Oxidized Low-Density Lipoproteins Facilitate Leukocyte Adhesion to Aortic Intima Without Affecting Endothelium-Dependent Relaxation
Role of P-Selectin
From the Departments of Medicine (B.Y., J.L.M.) and Pathology (S.K., J.B.H., C.S.), University of Florida College of Medicine, and the Veterans Affairs Medical Center, Gainesville, Fla.
Abstract 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
-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. These data show that cell adhesion to vascular
intima exposed to ox-LDL shows no temporal relation with attenuation of
NO activity, although inhibition of NO synthesis leads to leukocyte
deposition. P-selectin expression on vascular rings exposed to ox-LDL
appears to be the basis of leukocyte deposition.
Key Words: leukocytes • low-density lipoproteins • nitric oxide
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