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 beta2-integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) in cytokine-triggered firm leukocyte adhesion to arterial endothelium in vivo.


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).


CONCLUSIONS
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 beta2-integrin leukocyte extravasation in arterial injury and atherogenesis.
Schramm
R
R
Department of Thoracic and Cardiovascular Surgery, University of Saarland, 66421, Homburg/Saar, Germany. reneschramm@hotmail.com
Menger
M D
MD
Schaefers
H-J
HJ
Thorlacius
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis; D040881:CD11a Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D013997:Time Factors; D019076:Transgenes; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D040881:CD11a Antigen; D018925:Chemokines; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1