Vol 9: Neutrophil-Mediated Phagocytic Host Defense Defect in Myeloid Cftr-Inactivated Mice.Reportar como inadecuado



 Vol 9: Neutrophil-Mediated Phagocytic Host Defense Defect in Myeloid Cftr-Inactivated Mice.


Vol 9: Neutrophil-Mediated Phagocytic Host Defense Defect in Myeloid Cftr-Inactivated Mice. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Descargar gratis o leer online en formato PDF el libro: Vol 9: Neutrophil-Mediated Phagocytic Host Defense Defect in Myeloid Cftr-Inactivated Mice.
This article is from PLoS ONE, volume 9.AbstractCystic fibrosis CF is a common and deadly inherited disease, caused by mutations in the CFTR gene that encodes a cAMP-activated chloride channel. One outstanding manifestation of the disease is the persistent bacterial infection and inflammation in the lung, which claims over 90% of CF mortality. It has been debated whether neutrophil-mediated phagocytic innate immunity has any intrinsic defect that contributes to the host lung defense failure. Here we compared phagosomal CFTR targeting, hypochlorous acid HOCl production, and microbial killing of the neutrophils from myeloid Cftr-inactivated Myeloid-Cftr−-− mice and the non-inactivated control Cftrfl10 mice. We found that the mutant CFTR that lacked Exon-10 failed to target to the neutrophil phagosomes. This dysfunction resulted in impaired intraphagosomal HOCl production and neutrophil microbial killing. In vivo lung infection with a lethal dose of Pseudomonas aeruginosa caused significantly higher mortality in the myeloid CF mice than in the controls. The myeloid-Cftr−-− lungs were deficient in bacterial clearance, and had sustained neutrophilic inflammation and stalled transition from early to late immunity. These manifestations recapitulated the symptoms of human CF lungs. The data altogether suggest that myeloid CFTR expression is critical to normal host lung defense. CFTR dysfunction in neutrophils compromises the phagocytic innate immunity, which may predispose CF lungs to infection.



Autor: Ng, Hang Pong; Zhou, Yun; Song, Kejing; Hodges, Craig A.; Drumm, Mitchell L.; Wang, Guoshun

Fuente: https://archive.org/







Documentos relacionados