© 2000 American Heart Association, Inc.
Cellular Biology |
Direct Observations In Vivo on the Role of Endothelial Selectins and 
4 Integrin in Cytokine-Induced Leukocyte-Endothelium Interactions in the Mouse Aorta
From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Correspondence to Einar Eriksson, Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail einar.eriksson{at}fyfa.ki.se
Abstract—The molecular mechanisms
underlying leukocyte recruitment in large arteries have been
extensively studied using histological techniques on
fixed tissues. However, there are no reports that address the dynamics
of leukocyte recruitment in large arteries in vivo. We developed an
intravital microscopy technique for direct observation of
leukocyte-endothelium interactions in the mouse aorta.
Circulating leukocytes were labeled intravasally with rhodamine 6G and
microscopically visualized within the aorta, allowing direct
analysis of leukocyte rolling and adhesion. In untreated
vessels, leukocyte-endothelium interactions were
virtually absent. However, local pretreatment with cytokines
interleukin-1ß and tumor necrosis factor-
induced clear-cut
leukocyte rolling and adhesion, compatible with normal blood flow and
wall shear rate. High shear decreased rolling leukocyte flux and
increased leukocyte rolling velocity, thus decreasing the tendency for
firm adhesion. Leukocyte rolling was almost abolished by an antibody
blocking the function of P-selectin, whereas function-blocking
antibodies against E-selectin and the 4-integrin subunit
decreased rolling leukocyte flux to 51±34% (mean±SD) and 59±11% of
the value before antibody treatment, respectively. In addition,
inhibition of E-selectin function, but not of 4
integrin, resulted in increased leukocyte rolling velocity (from 48±32
to 71±32 µm per second). Taken together, we introduce the first
model for direct studies of leukocyte-endothelium
interactions in a large artery in vivo and demonstrate
cytokine-induced shear-sensitive leukocyte rolling that is
critically dependent on P-selectin and modulated by E-selectin and
4 integrin.
Key Words: leukocyte • rolling • intravital • atherosclerosis • cytokine
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