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

Alvaro Cervera*, Anna M. Planas, Carles Justicia, Xabier Urra, Jens C. Jensenius, Ferran Torres, Francisco Lozano, Angel Chamorro

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

103 Citations (Scopus)

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.

Original languageAmerican English
Article numbere8433
JournalPLoS ONE
Volume5
Issue number2
DOIs
Publication statusPublished - 3 Feb 2010

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