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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Spiller, Fernando Souto, Fabrício O. Silva, João S. Ryffel, Bernhard Cunha, Fernando Q. Borges, Vanessa F. Alves-Filho, José C. Trevelin, Silvia C. de Freitas, Andressa Carlos, Daniela
Description	Country affiliation: Brazil Author Affiliation: Carlos D ( Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.)
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 alloxan-induced diabetic and spontaneous NOD mice. Finally, diabetic W/W(v) mice had neutrophil migration to the peritoneal cavity, increased CXCR2 expression, and reduced bacteremia compared with diabetic WB/B6 mice. These results demonstrate that histamine released by MCs reduces diabetic host resistance to septic peritonitis in mice.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	3
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Diabetes Mellitus, Experimental Mortality G-protein-coupled Receptor Kinase 2 Metabolism Mast Cells Immunology Neutrophils Receptors, Interleukin-8b Alloxan Animals Bacteremia Drug Therapy Cell Movement Complications Microbiology Down-regulation Drug Effects Histamine Histamine H2 Antagonists Inflammation Mice Mice, Inbred Balb C Mice, Inbred Nod Receptors, Histamine H2 Sepsis Up-regulation P-methoxy-n-methylphenethylamine Pharmacology Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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