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The contribution of mannose binding lectin to reperfusion injury after ischemic stroke.

ABSTRACT: After complement system (CS) activation, the sequential production of complement products increases cell injury and death through opsonophagocytosis, cytolysis, adaptive, and inflammatory cell responses. These responses potentiate cerebral ischemia-reperfusion (IR) injury after ischemic stroke and reperfusion. Activation of the CS via mannose binding lectin (MBL)-initiated lectin pathway is known to increase tissue damage in response to IR in muscle, myocardium and intestine tissue. In contrast, the contribution of this pathway to cerebral IR injury, a neutrophil-mediated event, is less clear. Therefore, we investigated the potential protective role of MBL deficiency in neutrophil-mediated cerebral injury after IR. Using an intraluminal filament method, neutrophil activation and cerebral injury were compared between MBL-deficient and wild type C57Bl/6 mice subjected to 60 minutes of MCA ischemia and reperfusion. Systemic neutrophil activation was not decreased in MBL-deficient animals after IR. In MBL-deficient animals, cerebral injury was significantly decreased only in the striatum (p < 0.05). Despite MBL deficiency, C3 depositions were evident in the injured hemisphere during reperfusion. These results indicate that while MBL deficiency results in a modest protection of a sub-cortical brain region during IR, redundant complement pathway activation may overwhelm further beneficial effects of MBL deficiency during reperfusion.

SUBMITTER: Morrison H

PROVIDER: S-EPMC3512100 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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The contribution of mannose binding lectin to reperfusion injury after ischemic stroke.

Morrison Helena H Frye Jennifer J Davis-Gorman Grace G Funk Janet J McDonagh Paul P Stahl Gregory G Ritter Leslie L

Current neurovascular research 20110201 1

After complement system (CS) activation, the sequential production of complement products increases cell injury and death through opsonophagocytosis, cytolysis, adaptive, and inflammatory cell responses. These responses potentiate cerebral ischemia-reperfusion (IR) injury after ischemic stroke and reperfusion. Activation of the CS via mannose binding lectin (MBL)-initiated lectin pathway is known to increase tissue damage in response to IR in muscle, myocardium and intestine tissue. In contrast, ...[more]

PMID: 21208161

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Project description:ObjectivesCutaneous ischemia/reperfusion (CI/R) injury has shown to play a significant role in chronic wounds such as decubitus ulcers, diabetic foot ulcers, atherosclerotic lesions, and venous stasis wounds. CI/R also plays a role in free tissue transfer in reconstructive microsurgery and has been linked to clinical burn-depth progression after thermal injury. While the role of the complement system has been elucidated in multiple organ systems, evidence is lacking with respect to its role in the skin. Therefore, we evaluated the role of the complement system in CI/R injury.MethodsUsing a single pedicle skin flap mouse model of acute CI/R, we performed CI/R in wild-type (WT) mice and complement knock out (KO) mice, deficient in either C1q (C1q KO; classical pathway inhibition), mannose-binding lectin (MBL null; lectin pathway inhibition) or factor B (H2Bf KO; alternative pathway inhibition). Following 10 h ischemia and 7 days reperfusion, mice were sacrificed, flaps harvested and flap viability assessed via Image J software. The flap necrotic area was expressed as % total flap area. In another group, mice were sacrificed following CI/R with 10 h ischemia and 48 h reperfusion. Two cranial skin flap samples were taken for gene expression analysis of IL1b, IL6, TNFα, ICAM1, VCAM1, IL10, IL13 using real-time polymerase chain reaction (RT-PCR).ResultsFollowing CI/R, MBL null mice had a statistically significant smaller %necrotic flap area compared to WT mice (10.6 vs. 43.1%; p<0.05) suggesting protection from CI/R. A significantly reduced mean %necrotic flap area was not seen in either C1q KO or H2Bf KO mice relative to WT (22.9 and 31.3 vs. 43.1%; p=0.08 and p=0.244, respectively). There were no statistically significant differences between groups for markers of inflammation (TNFα, ICAM1, VCAM1, IL1b, IL6). In contrast, mRNA levels of IL10, a regulator of inflammation, were significantly increased in the MBL null group (p=0.047).ConclusionsWe demonstrated for the first time a significant role of MBL and the lectin complement pathway in ischemia/reperfusion injury of the skin and a potential role for IL10 in attenuating CI/R injury, as IL10 levels were significantly increased in the tissue from the CI/R-protected MBL null group.

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The contribution of mannose binding lectin to reperfusion injury after ischemic stroke.

Publications

The contribution of mannose binding lectin to reperfusion injury after ischemic stroke.

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