INVESTIGADORES
SOTOMAYOR Claudia Elena
artículos
Título:
Protective phenotypes of club cells and alveolar macrophages are favored as part of endotoxin-mediated prevention of asthma
Autor/es:
GARCÍA LN; LEIMGRUBER C; URIBE ECHEVARRÍA EM; ACOSTA PL; BRAHAMIAN JM,; POLACK FP; MIRÓ MS,; QUINTAR A; SOTOMAYOR CE; MALDONADO C
Revista:
EXPERIMENTAL BIOLOGY AND MEDICINE
Editorial:
SOC EXPERIMENTAL BIOLOGY MEDICINE
Referencias:
Lugar: Maywood; Año: 2014 p. 1 - 13
ISSN:
1535-3702
Resumen:
Atopic asthma is a chronic allergic disease that involves T-helper type 2 (Th2)-inflammation and airway remodeling. Bronchiolar
club cells (CC) and alveolar macrophages (AM) are sentinel cells of airway barrier against inhaled injuries, where allergy induces
mucous metaplasia of CC and the alternative activation of AM, which compromise host defense mechanisms and amplify Th2-
inflammation. As there is evidence that high levels of environmental endotoxin modulates asthma, the goal of this study was to
evaluate if the activation of local host defenses by Lipopolysaccharide (LPS) previous to allergy development can contribute to
preserving CC and AM protective phenotypes. Endotoxin stimulus before allergen exposition reduced hallmarks of allergic inflammation
including eosinophil influx, Interleukin-4 and airway hyperreactivity, while the T-helper type 1 related cytokines IL-12 and
Interferon-g were enhanced. This response was accompanied by the preservation of the normal CC phenotype and the antiallergic
proteins Club Cell Secretory Protein (CCSP) and Surfactant-D, thereby leading to lower levels of CC metaplasia and
preventing the increase of the pro-Th2 cytokine Thymic stromal lymphopoietin. In addition, classically activated alveolar macrophages
expressing nitric oxide were promoted over the alternatively activated ones that expressed arginase-1. We verified that
LPS induced a long-term overexpression of CCSP and the innate immune markers Toll-like receptor 4, and Tumor Necrosis
Factor-a, changes that were preserved in spite of the allergen challenge. These results demonstrate that LPS pre-exposition
modifies the local bronchioalveolar microenvironment by inducing natural anti-allergic mechanisms while reducing local factors
that drive Th2 type responses, thus modulating allergic inflammation.