Neutrophils in the Obese Lung: A Mechanistic Study in a Mouse Model of Metabolic Syndrome.

FLORENCIA M SOLER GARCIA ; NIDIA N GOMEZ ; GOMEZ-MEJIBA S.E; MARCOS D MUNOZ ; LUCIA B FUENTES; SAURABH CHATTERJEE; MARIA C DELLA VEDOVA ; LUCAS D SANTILLAN ; SUSANA E SIEWERT; DARIO C RAMIREZ

Congreso; SFRBM; 2016

">410Neutrophils in the Obese Lung: A Mechanistic Studyin a Mouse Model of Metabolic SyndromeMaria C Della Vedova1, Marcos D Munoz1, Florencia M Soler Garcia1,Lucas D Santillan1, Lucia B Fuentes1, Nidia N Gomez1, Susana ESiewert1, Saurabh Chatterjee2, Sandra E Gomez Mejiba1, and Dario CRamirez11CONICET-UNSL, San Luis, Argentina, 2Environmental Health &Disease Laboratory, University of South Carolina, Columbia, USAThe metabolic syndrome (MS) is a deadly metabolic abnormalityassociated to obesity. The pulmonary microvasculature is a sink ofcirculating neutrophils; as well as this is highly sensitive to smallchanges in the systemic oxidative/inflammatory profile, as occur inchronic inflammatory diseases, such as obesity. Previously, wehave characterized a MS-mouse model in which animals were fedfor 16 weeks a 22% p/p chicken-fat rich diet and 10 % fructose inthe drinking water. These animals show several features of MSincluding obesity, central adiposity, insulin resistance (IR),hypertension, dyslipidemia and streatohepatitis. Using this modelwe envisioned to test whether MS predisposes to pulmonaryretention/activation of neutrophils and how it affects whole-body IR.To accomplish this goal we studied MS and control mice (B6 micefed for 16 weeks with low-fat diet/tap water). MS mice had more IRthan control mice. MS mice had also higher concentration ofcirculating inflammatory mediators than control mice. The lungtissue of MS mice was lighter and expressed more inflammationmediators (TNF-α; IL-6 and inducible nitric oxide) than the controllung. The lung of MS mice had more neutrophils (NIMP-14+ cells),myeloperoxidase (MPO) activity and chlorotyrosine than controlmice. ICAM-1 expression in MS mice?s lung tissue was higher thancontrol mice. In relation to control mice, intratracheal instillation(ITI) 2.5 ug lipopolysaccharide (LPS)/mouse to MS mice causedmore retention/activation of neutrophils, ICAM-1 expression, MPOactivity, chlorotyrosine, circulating inflammatory mediators and alsoworsened IR. These effects where damped by ITI of 5 nmol of 5,5-dimetil-1-pirrolina N-oxido/mouse. Our data suggest thatretention/activation of neutrophils in the lung may be a potentialtherapeutic target to reduce IR and other complications of obesity.Supported by PROICO 2-3214 & PICT-2014-3369 (toDCR),PROICO 10-0414 (ToSEGM) and PIP2015-2017-112215-0100603CO (To DCR, SEA & SEGM).doi: 10.1016/j.freeradbiomed.2016.10.451