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Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
1Correspondence: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail: einar.eriksson{at}fyfa.ki.se
Leukocyte infiltration in atherosclerosis has been extensively
investigated by using histological techniques on fixed tissues. In this
study, intravital microscopic observations of leukocyte recruitment in
the aorta of atherosclerotic mice were performed. Interactions between
leukocytes and atherosclerotic endothelium were highly transient,
thereby limiting the ability for rolling leukocytes to firmly adhere.
Leukocyte rolling was abolished by function inhibition of P-selectin
(P<0.001, n=8), whereas antibody
blockage of E-selectin (n=10) decreased rolling
leukocyte flux to 51 ± 9.9% (mean±SE,
P<0.01) and increased leukocyte rolling velocity to
162 ± 18% (P<0.01) of pretreatment values.
Notably, function inhibition of the integrin 
4 subunit
(n=5) had no effect on rolling flux (107±25%,
P=0.782) or rolling velocity (89±6.1%,
P=0.147), despite endothelial expression of vascular
cell adhesion molecule 1 (VCAM-1). Leukocytes interacting with
atherosclerotic endothelium were predominantly neutrophils, because
treatment with antineutrophil serum decreased rolling and neutrophil
counts in peripheral blood to the same extent. In conclusion, we
present the first direct observations of atherosclerosis in
vivo. We show that transient dynamics of leukocyte-endothelium
interactions are important regulators of arterial leukocyte recruitment
and that leukocyte rolling in atherosclerosis is critically dependent
on the endothelial selectins. This experimental technique and the data
presented introduce a novel perspective for the study of
pathophysiological events involved in large-vessel disease.—Eriksson,
E. E., Xie, X., Werr, J., Thoren, P., Lindbom, L. Direct viewing
of atherosclerosis in vivo: plaque invasion
by leukocytes is initiated by the endothelial selectins.
Key Words: intravital • atherosclerosis • inflammation • selectin • neutrophils
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