Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.

PLoS One

Comprehensive Stroke Center, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Medical School, University of Barcelona, Barcelona, Spain.

Published: February 2010

AI Article Synopsis

  • The complement system plays a crucial role in innate immunity and contributes to brain damage during strokes, specifically through the lectin pathway initiated by mannose-binding lectin (MBL) and associated proteases.
  • Research on MBL-null mice showed that they had smaller brain infarctions and better recovery compared to wild-type mice, and adding recombinant human MBL increased damage, suggesting a harmful effect of MBL during stroke.
  • Clinical analysis of stroke patients revealed that those with a genetically defined MBL-deficiency had improved outcomes, indicating that MBL plays a detrimental role in stroke recovery.

Article Abstract

Background: The complement system is a major effector of innate immunity that has been involved in stroke brain damage. Complement activation occurs through the classical, alternative and lectin pathways. The latter is initiated by mannose-binding lectin (MBL) and MBL-associated serine proteases (MASPs). Here we investigated whether the lectin pathway contributes to stroke outcome in mice and humans.

Methodology/principal Findings: Focal cerebral ischemia/reperfusion in MBL-null mice induced smaller infarctions, better functional outcome, and diminished C3 deposition and neutrophil infiltration than in wild-type mice. Accordingly, reconstitution of MBL-null mice with recombinant human MBL (rhMBL) enhanced brain damage. In order to investigate the clinical relevance of these experimental observations, a study of MBL2 and MASP-2 gene polymorphism rendering the lectin pathway dysfunctional was performed in 135 stroke patients. In logistic regression adjusted for age, gender and initial stroke severity, unfavourable outcome at 3 months was associated with MBL-sufficient genotype (OR 10.85, p = 0.008) and circulating MBL levels (OR 1.29, p = 0.04). Individuals carrying MBL-low genotypes (17.8%) had lower C3, C4, and CRP levels, and the proinflammatory cytokine profile was attenuated versus MBL-sufficient genotypes.

Conclusions/significance: In conclusion, genetically defined MBL-deficiency is associated with a better outcome after acute stroke in mice and humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815773PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008433PLOS

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