Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice.
Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChT(KD)) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChT(KD) in comparison with WT mice. VAChT(KD) mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.
Flávio Almeida
FA
Amaral
Caio Tavares
CT
Fagundes
Aline Silva
AS
Miranda
Vivian Vasconceios
VV
Costa
Livia
L
Resende
Danielle da
Dd
Gloria de Souza
Vania Ferreira
VF
Prado
Mauro Martins
MM
Teixeira
Marco Antonio
MA
Maximo Prado
Laboratório Interdisciplinar de Investigação Médica, Room 281, Faculdade de Medicina, UFMG. Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, Brasil. 30130-100. altexr@gmail.com.
Antonio Lucio
AL
Teixeira
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D053706:Typhlitis / Q000209:etiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000172:deficiency / Q000235:genetics
D054377:Chemokine CXCL12; D018722:Nicotinic Agonists; C493460:Slc18a3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D050494:Vesicular Acetylcholine Transport Proteins; D009538:Nicotine; D000109:Acetylcholine