| First Author | Cervera A | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 2 | Pages | e8433 |
| PubMed ID | 20140243 | Mgi Jnum | J:158006 |
| Mgi Id | MGI:4437513 | Doi | 10.1371/journal.pone.0008433 |
| Citation | Cervera A, et al. (2010) Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PLoS One 5(2):e8433 |
| abstractText | 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. |
