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

<h4>Background</h4>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 s...

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Autores principales:	Alvaro Cervera, Anna M Planas, Carles Justicia, Xabier Urra, Jens C Jensenius, Ferran Torres, Francisco Lozano, Angel Chamorro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75a92e0934394587a0d82e3a35f0296a
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spelling	oai:doaj.org-article:75a92e0934394587a0d82e3a35f0296a2021-11-25T06:26:10ZGenetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.1932-620310.1371/journal.pone.0008433https://doaj.org/article/75a92e0934394587a0d82e3a35f0296a2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20140243/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>In conclusion, genetically defined MBL-deficiency is associated with a better outcome after acute stroke in mice and humans.Alvaro CerveraAnna M PlanasCarles JusticiaXabier UrraJens C JenseniusFerran TorresFrancisco LozanoAngel ChamorroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e8433 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alvaro Cervera Anna M Planas Carles Justicia Xabier Urra Jens C Jensenius Ferran Torres Francisco Lozano Angel Chamorro Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>In conclusion, genetically defined MBL-deficiency is associated with a better outcome after acute stroke in mice and humans.
format	article
author	Alvaro Cervera Anna M Planas Carles Justicia Xabier Urra Jens C Jensenius Ferran Torres Francisco Lozano Angel Chamorro
author_facet	Alvaro Cervera Anna M Planas Carles Justicia Xabier Urra Jens C Jensenius Ferran Torres Francisco Lozano Angel Chamorro
author_sort	Alvaro Cervera
title	Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
title_short	Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
title_full	Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
title_fullStr	Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
title_full_unstemmed	Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
title_sort	genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/75a92e0934394587a0d82e3a35f0296a
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Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke.

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