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.
Arumugam
Thiruma V
TV
Dept. of Molecular and Cellular Physiology, Louisiana State Univ. Health Sciences Center, 1500 Kings Highway, Shreveport, LA 71130, USA.
Salter
James W
JW
Chidlow
John H
JH
Ballantyne
Christie M
CM
Kevil
Christopher G
CG
Granger
D Neil
DN
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