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oai:uvadoc.uva.es:10324/98172021-06-23T09:49:15Zcom_10324_1133com_10324_931com_10324_894col_10324_1209

00925njm 22002777a 4500 dc Simarro Grande, María author Giannattasio, Giorgio author Benarafa, Charaf author Subramanian, Kulandayan K. author Ishizawar, Rumey author Balestrieri, Barbara author Andersson, Emma M. author Luo, Hongbo R. author Orduña Domingo, Antonio author Boyce, Joshua author Fuente García, Miguel Ángel de la author 2010 We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice (FAST−/−) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. FAST−/− mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST−/− mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because FAST−/− neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation. J Immunol. 2010; 184(9): 5325–5332. 0022-1767 http://uvadoc.uva.es/handle/10324/9817 10.4049/jimmunol.1000104 5325 9 5332 Journal of Immunology 184 Sistema inmunitario-Enfermedades Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation