Leukocyte adhesion in aorta and femoral artery in vivo is mediated by LFA-1

• Objective: Cytokine-induced recruitment of leukocytes is an early feature during arterial injury and atherosclerotic plaque formation. The aim of this study was to analyze the role of the beta(2)-integrin lymphocyte function-associated antigen-1 (LFA- 1; CD11a/CD18) in cytokine-triggered firm leukocyte adhesion to arterial endothelium in vivo. Material and Methods: Intravital fluorescence microscopy was used to study leukocyte firm adhesion in the mouse aorta and femoral artery in response to combined local challenge with TNF-alpha and IL-1beta. Results: In wild-type (WT) mice, cytokine stimulation resulted in firm adhesion of 14.6 +/- 2.8 and 11.3 +/- 1.3 leukocytes/mm along the endothelium in the aorta and femoral artery (P < 0.05 vs. PBS-treated controls, n = 5-6). Notably, the number of firmly adherent leukocytes in aorta and femoral artery of cytokine-stimulated LFA-1-deficient animals was reduced by 54% and 92% indicating an important role of LFA-1 in leukocyte adhesion to arterial endothelium (P < 0.05 vs. controls, n = 5-6). In addition, pretreatment of WT mice with a monoclonal antibody (mAb) directed against murine LFA-1 attenuated the leukocyte adhesive response by 60% and 86% in aorta and femoral artery, respectively (P < 0.05 vs. control mAb-treated WT, n = 5-12). Conclusion: These novel data demonstrate that cytokine-induced firm leukocyte adhesion in the mouse aorta and femoral artery is LFA-1-dependent in vivo, which may implicate an important role for this β(2)-integrin leukocyte extravasation. in arterial injury and atherogenesis.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Keyword

leukocyte recruitment

beta(2)-integrins

inflammation

atherosclerosis

cytokines

Publication and Content Type

art (subject category)

ref (subject category)