CHARACTERIZATION OF THE MECHANISM THAT TARGETS INTERLEUKIN-1BETA TOWARDS AUTOPHAGOSOMES FOR SECRETION

KEITELMAN, IRENE A.; SABBIONE, FLORENCIA; GUZMAN, MAURICIO; GERBER, PEHUÉN PEREYRA; TREVANI, ANALÍA S.; SHIROMIZU, MAIUMI; MIGLIO, M.; JANCIC, CAROLINA; OSTROWSKI, MATÍAS; ZGAJNAR, NADIA R.; F. FUENTES; GALLETTI, JEREMÍAS G.; GALIGNANA M

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2018

IL-1β is a major proinflammatory cytokine synthesized in the cytoplasm as an inactive precursor that is activated by proteolytic cleavage. It is a leaderless cytosolic protein that is secreted by unconventional mechanisms different from the classical ER-Golgi pathway.Our previous studies indicated that neutrophil cytoplasmic IL-1βis targeted to an autophagic compartment and is secreted by anunconventional secretory autophagic mechanism. The aim of thisstudy was to gain insights into the mechanisms involved in IL-1βloading into the vesicles from which IL-1β is going to be secretedby human neutrophils. Neutrophils were isolated from healthy donors and stimulated for 5 h with LPS+ATP. We first investigated byELISA if IL-1β is released inside extracellular vesicles. We foundthat 783±223 pg/ml of IL-1β were released to supernatants devoidof extracellular vesicles and 47±14 pg/ml were released inside extracellular vesicles (n=4; p