Histamine h2 receptor signaling in the pathogenesis of sepsis: studies in a murine diabetes model

The Journal of Immunology : Official Journal of the American Association of Immunologists
Daniela CarlosFernando Q Cunha

Abstract

Type 1 diabetes enhances susceptibility to infection and favors the sepsis development. In addition, diabetic mice produced higher levels of histamine in several tissues and in the blood after LPS stimulation than nondiabetic mice. In this study, we aimed to explore the role of mast cells (MCs) and histamine in neutrophil migration and, consequently, infection control in diabetic mice with mild sepsis (MS) induced by cecum ligation and puncture. We used female BALB/c, MC-sufficient (WB/B6), MC-deficient (W/W(v)), and NOD mice. Diabetic mice given MS displayed 100% mortality within 24 h, whereas all nondiabetic mice survived for at least 5 d. The mortality rate of diabetic mice was reduced to 57% after the depletion of MC granules with compound 48/80. Moreover, this pretreatment increased neutrophil migration to the focus of infection, which reduced systemic inflammatory response and bacteremia. The downregulation of CXCR2 and upregulation of G protein-coupled receptor kinase 2 in neutrophils was prevented by pretreatment of diabetic mice given MS with compound 48/80. In addition, blocking the histamine H2 receptor restored neutrophil migration, enhanced CXCR2 expression, decreased bacteremia, and improved sepsis survival in all...Continue Reading

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Citations

Jul 25, 2014·World Journal of Gastroenterology : WJG·Ji Eun KwonHyun Chae Jung
May 29, 2014·Expert Review of Clinical Immunology·Fabiane SônegoFernando Queiróz Cunha
Oct 30, 2016·Shock·Silvia C TrevelinFernando Q Cunha
Sep 19, 2018·Mediators of Inflammation·Anna Cláudia Calvielli Castelo BrancoMaria Notomi Sato

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