Contributions of LFA-1 and Mac-1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion.
Although the beta2-integrins have been implicated in the pathogenesis of cerebral ischemia-reperfusion (I/R) injury, the relative contributions of the alpha-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 alpha-subunits of the beta2-integrins contribute to the brain injury and blood cell-vessel wall interactions that are associated with transient focal cerebral ischemia.
Dept. of Molecular and Cellular Physiology, Louisiana State Univ. Health Sciences Center, 1500 Kings Highway, Shreveport, LA 71130, USA.
Thiruma V
TV
Arumugam
James W
JW
Salter
John H
JH
Chidlow
Christie M
CM
Ballantyne
Christopher G
CG
Kevil
D Neil
DN
Granger
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D002450:Cell Communication; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008833:Microcirculation
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen