Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo.
In the multistep process of leukocyte extravasation, the mechanisms by which leukocytes establish the initial contact with the endothelium are unclear. In parallel, there is a controversy regarding the role for L-selectin in leukocyte recruitment. Here, using intravital microscopy in the mouse, we investigated leukocyte capture from the free flow directly to the endothelium (primary capture), and capture mediated through interactions with rolling leukocytes (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on atherosclerotic lesions in the aorta. Capture was more prominent in arterial vessels compared with venules. In venules, the incidence of capture increased with increasing vessel diameter and wall shear rate. Secondary capture required a minimum rolling leukocyte flux and contributed by approximately 20-50% of total capture in all studied vessel types. In arteries, secondary capture induced formation of clusters and strings of rolling leukocytes. Function inhibition of L-selectin blocked secondary capture and thereby decreased the flux of rolling leukocytes in arterial vessels and in large (>45 microm in diameter), but not small (<45 microm), venules. These findings demonstrate the importance of leukocyte capture from the free flow in vivo. The different impact of blockage of secondary capture in venules of distinct diameter range, rolling flux, and wall shear rate provides explanations for the controversy regarding the role of L-selectin in various situations of leukocyte recruitment. What is more, secondary capture occurs on atherosclerotic lesions, a fact that provides the first evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.
Eriksson
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Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. einar.eriksson@fyfa.ki.se
Xie
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Werr
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Thoren
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Lindbom
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D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D002465:Cell Movement; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D019041:L-Selectin / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D014699:Venules / Q000473:pathology / Q000503:physiopathology
D019041:L-Selectin