Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury.
OBJECTIVE
Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte beta2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1.


METHODS
Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1-deficient (n=12) and wild-type (n=11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils.


RESULTS
Compared with the wild-type cohort, Mac-1-deficient mice had a 26% reduction in infarction volume (P<0.05). This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups.


CONCLUSIONS
Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1-deficient mice.
Soriano
S G
SG
Department of Anesthesia, Children's Hospital, Boston, MA 02115, USA. soriano@A1.tch.harvard.edu
Coxon
A
A
Wang
Y F
YF
Frosch
M P
MP
Lipton
S A
SA
Hickey
P R
PR
Mayadas
T N
TN
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics* / Q000378:metabolism; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000235:genetics; D002633:Chemotaxis / Q000502:physiology; D004198:Disease Susceptibility; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1