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Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins
Author(s) -
ERIKSSON EINAR E.,
XIE XUN,
WERR JOACHIM,
THOREN PETER,
LINDBOM LENNART
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0537com
Subject(s) - selectin , endothelium , intravital microscopy , in vivo , cell adhesion molecule , inflammation , infiltration (hvac) , integrin , aorta , p selectin , immunology , pathophysiology , endothelial stem cell , chemistry , pathology , platelet , medicine , cell , biology , in vitro , platelet activation , biochemistry , physics , microbiology and biotechnology , thermodynamics
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 α 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. FASEB J . 15, 1149‐1157 (2001)