Recombinant human β-defensin 2 delivery improves smoking-induced lung neutrophilia and bacterial exacerbation.

Autor: Milad, Nadia, Pineault, Marie, Bouffard, Gabrielle, Maranda-Robitaille, Michaël, Lechasseur, Ariane, Beaulieu, Marie-Josée, Aubin, Sophie, Jensen, Benjamin A. H., Morissette, Mathieu C.
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Zdroj: American Journal of Physiology: Lung Cellular & Molecular Physiology; Jul2022, Vol. 323 Issue 1, pL37-L47, 11p
Abstrakt: Treatment of the cigarette smoke-associated lung diseases, such as chronic obstructive pulmonary disease (COPD), has largely focused on broad-spectrum anti-inflammatory therapies. However, these therapies, such as high-dose inhaled corticosteroids, enhance patient susceptibility to lung infection and exacerbation. Our objective was to assess whether the cationic host defense peptide, human b-defensin 2 (hBD-2), can simultaneously reduce pulmonary inflammation in cigarette smoke-exposed mice while maintaining immune competence during bacterial exacerbation. Mice were exposed to cigarette smoke acutely (4 days) or chronically (5 days/wk for 7 wk) and administered hBD-2 intranasally or by gavage. In a separate model of acute exacerbation, chronically exposed mice treated with hBD-2 were infected with nontypeable Haemophilus influenzae before euthanasia. In the acute exposure model, cigarette smoke-associated pulmonary neutrophilia was significantly blunted by both local and systemic hBD-2 administration. Similarly, chronically exposed mice administered hBD-2 therapeutically exhibited reduced pulmonary neutrophil infiltration and downregulated proinflammatory signaling in the lungs compared with vehicle-treated mice. Finally, in a model of acute bacterial exacerbation, hBD-2 administration effectively limited neutrophil infiltration in the lungs while markedly reducing pulmonary bacterial load. This study shows that hBD-2 treatment can significantly attenuate lung neutrophilia induced by cigarette smoke exposure while preserving immune competence and promoting an appropriate host-defense response to bacterial stimuli. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index