Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation

Simarro, Maria; Giannattasio, Giorgio; De la Fuente, Miguel A; Benarafa, Charaf; Subramanian, Kulandayan K; Ishizawar, Rumey; Balestrieri, Barbara; Andersson, Emma M; Luo, Hongbo R; Orduña, Antonio; Boyce, Joshua; Anderson, Paul (2010). Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation. Journal of immunology, 184(9), pp. 5325-32. Bethesda, Md.: American Association of Immunologists 10.4049/jimmunol.1000104

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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-alpha 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Benarafa, Charaf




American Association of Immunologists




Factscience Import

Date Deposited:

04 Oct 2013 14:11

Last Modified:

04 May 2014 23:05

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https://boris.unibe.ch/id/eprint/2151 (FactScience: 204407)

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