NEUTROPHIL EXTRACELLULAR TRAPS RELEASED IN RESPONSE OF CIGARETTE SMOKE EXTRACT INCREASE THE SECRETION OF PROINFLAMMATORY CYTOKINES BY HUMAN ALVEOLAR EPITHELIAL CELLS.

SABBIONE FLORENCIA; KEITELMAN IRENE; GUZMÁN MAURICIO; GALLETTI JEREMÍAS GASTÓN; FERRERO, MARIANA; BALDI, PABLO; TOWSTYKA, NADIA; GIORDANO MIRTA NILDA; JANCIC, CAROLINA; TREVANI ANALÍA SILVINA

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016

Sociedad Argentina de Inmunología

Cigarette smoMing is a major cause of chronic obstructivepulmonary disease. )as phase of cigarette smoMe CS can reach the alveolar epithelium inducing the secretion of chemoMinesand cytoMines that contribute to recruit neutrophils 2/0 intothe airYay lumen. +n response to diverse stimuli, 2/0 releaseneutrophil extracellular traps 0ET through a process called 0ETosis.Previous studies determined that CS and uric acid (UA), amajor &A/2 found at high concentrations in lungs of patients Yithacute lung injury, can induce 0ETosis. The aim of this study Yasto determine if a short exposure to CS is able to induce 0ETosis,and if these 0ET induce proinflammatory cytoMine secretion byalveolar epithelial cells, comparing their effects Yith those producedby 0ET released in response to 7A mg/dl. CS extractCSE prepared according to a standard method from cigarettescontaining an equivalent of . mg/ml tar Yas used at . 2/0Yere incubated Yith or Yithout stimuli for h, then Yashed andcultured for more hours at uC. 0ET Yere identified by confocalmicroscopy by colocalization of &0A Yith myeloperoxidase. Shortexposure to both stimuli induced 0ETosis. 0ET released by 62/0 Yere isolated and added to A epithelial cell monolayers.$oth CSE and 7Ainduced 0ET significantly increased thesecretion of +L and +L p. n, and +Lb n by Aas compared to that induced by supernatants from unstimulated2/0 and basal conditions. These effects Yere not observed Yithsupernatants from CSstimulated 2/0 pretreated Yith the 0ETosisinhibitor CLamidine z/ n. These findings suggestthat CSE might also promote alveolar inflammation by triggering0ETosis. Together Yith our previous findings indicating similarproperties of 0ET induced by monosodium urate crystals, theseresults alsosuggest that 0ET exert proinflammatory effects onepithelial cells independently of the sterile stimulus that inducedtheir release.