Contributions of LFA-1 and Mac-1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion

• Published in: American journal of physiology. Heart and circulatory physiology 2004-12, Vol.287 (6), p.H2555-H2560
• Main Authors: Arumugam, Thiruma V, Salter, James W, Chidlow, John H, Ballantyne, Christie M, Kevil, Christopher G, Granger, D. Neil
• Format: Article
• Language: English
• Subjects: Animals; Blood Platelets - cytology; Blood Platelets - physiology; Cell Communication; Cerebrovascular Circulation; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Infarction, Middle Cerebral Artery - mortality; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - physiopathology; Leukocytes - cytology; Leukocytes - physiology; Lymphocyte Function-Associated Antigen-1 - genetics; Lymphocyte Function-Associated Antigen-1 - metabolism; Macrophage-1 Antigen - genetics; Macrophage-1 Antigen - metabolism; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microcirculation
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00588.2004

Departments of 1 Molecular and Cellular Physiology and 2 Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, 71130; and 3 Department of Medicine, Baylor College of Medicine, Houston, Texas 77030 Submitted 14 June 2004 ; accepted in final form 9 August 2004 Although the 2 -integrins have been implicated in the pathogenesis of cerebral ischemia-reperfusion (I/R) injury, the relative contributions of the -subunits to the pathogenesis of ischemic stroke remains unclear. The objective of this study was to determine whether and how genetic deficiency of either lymphocyte function-associated antigen-1 (LFA-1) or macrophage-1 (Mac-1) alters the blood cell-endothelial cell interactions, tissue injury, and organ dysfunction in the mouse brain exposed to focal I/R. Middle cerebral artery occlusion was induced for 1 h (followed by either 4 or 24 h of reperfusion) in wild-type mice and in mice with null mutations for either LFA-1 or Mac-1. Neurological deficit and infarct volume were monitored for 24 h after reperfusion. Platelet- and leukocyte-vessel wall adhesive interactions were monitored in cortical venules by intravital microscopy. Mice with null mutations for LFA-1 or Mac-1 exhibited significant reductions in infarct volume. This was associated with a significant improvement in the I/R-induced neurological deficit. Leukocyte adhesion in cerebral venules did not differ between wild-type and mutant mice at 4 h after reperfusion. However, after 24 h of reperfusion, leukocyte adhesion was reduced in both LFA-1- and Mac-1-deficient mice compared with their wild-type counterparts. Platelet adhesion was also reduced at both 4 and 24 h after reperfusion in the LFA-1- and Mac-1-deficient mice. These findings indicate that both -subunits of the 2 -integrins contribute to the brain injury and blood cell-vessel wall interactions that are associated with transient focal cerebral ischemia. lymphocyte function-associated antigen-1; macrophage-1; ischemic stroke; 2 -integrins; platelet Address for reprint requests and other correspondence: D. N. Granger, Dept. of Molecular and Cellular Physiology, Louisiana State Univ. Health Sciences Center, 1500 Kings Highway, Shreveport, LA 71130 (E-mail: dgrang{at}lsuhsc.edu )