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Título : M1 macrophage polarization is dependent on TRPC1-mediated calcium entry
Autor : Chauhan, Arun 
Sun, Yuyang 
Sukumaran, Pramod 
Quenum Zangbede, Fredice O. 
Jondle, Christopher N. 
Sharma, Atul 
Evans, Dustin L. 
Chauhan, Pooja 
Szlabick, Randolph E. 
Aaland, Mary O. 
Birnbaumer, Lutz 
Sharma, Jyotika 
Singh, Brij B. 
Mishra, Bibhuti B. 
Palabras clave : INMUNOLOGIASISTEMA INMUNOLOGICOCALCIOSEPSIS
Fecha de publicación : 2018
Editorial : Elsevier (Cell Press)
Cita : Chauhan A, Sun Y, Sukumaran P, et al. M1 macrophage polarization is dependent on TRPC1-mediated calcium entry. iScience. 2018;8:85-102. doi:10.1016/j.isci.2018.09.014 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8685
Resumen : Abstract: Macrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated Ca2+ entry and inhibition of Ca2+ entry impairs polarization to M1 inflammatory phenotype. In vitro and in vivo functional analyses revealed ORAI1 to be a primary contributor to basal Ca2+ influx in macrophages, whereas IFNγ-induced Ca2+ influx was mediated by TRPC1. Deficiency of TRPC1 displayed abrogated IFNγ-induced M1 inflammatory mediators in macrophages. In a preclinical model of peritonitis by Klebsiella pneumoniae infection, macrophages showed increased Ca2+ influx, which was TRPC1 dependent. Macrophages from infected TRPC1-/- mice showed inhibited expression of M1-associated signature molecules. Furthermore, in human patients with systemic inflammatory response syndrome, the level of TRPC1 expression in circulating macrophages directly correlated with M1 inflammatory mediators. Overall, TRPC1-mediated Ca2+ influx is essential for the induction/shaping of macrophage polarization to M1 inflammatory phenotype.
URI : https://repositorio.uca.edu.ar/handle/123456789/8685
ISSN : 2589-0042
Disciplina: MEDICINA
DOI: 10.1016/j.isci.2018.09.014
Derechos: Acceso Abierto
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