Impact of aging on inflammatory and immune responses during elastin peptide-induced murine emphysema

Abstract : Deterioration of lung functions and degradation of elastin fibers with age are accelerated during chronic obstructive pulmonary disease (COPD). Excessive genesis of soluble elastin peptides (EP) is a key factor in the pathophysiology of COPD. We have previously demonstrated that 6-wk-old mice exhibited emphysematous structural changes associated with proinflammatory immune response after EP instillation. In this study, we investigated the consequences of aging on inflammatory, immune, and histological criteria associated with murine emphysema progression after EP exposure. Young (6 wk old) and elderly (15 mo old) C57BL/6J mice were endotracheally instilled with EP, and, at various time points after treatment, the inflammatory cell profiles from bronchoalveolar lavage fluids (BALF) and the T-lymphocyte phenotypes, at local and systemic levels, were analyzed by flow cytometry. Lungs were also prepared to allow morphological and histological analysis by confocal microscopy. Elderly mice exhibited an earlier development of pulmonary emphysema, characterized by an increase of the inflammatory and lymphocytic infiltrates, extracellular matrix breakdown, and airspace enlargement compared with young mice. This age-dependent parenchymal tissue remodeling was associated with an increase of the matrix metalloproteinase expressions and desmosine levels in BALF and/or sera of EP-treated mice. In addition, both the proportion of CD4+CD28- and CD8+CD28- T cells in the tissues of EP-treated mice and the interferon-γ levels in the EP-specific memory T-cell clones were significantly higher in elderly versus younger mice. This study demonstrates that aging accelerates emphysema development and that this effect is linked to increased EP production and their effects on inflammatory and immune response.
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Submitted on : Thursday, August 29, 2019 - 4:42:56 PM
Last modification on : Friday, August 30, 2019 - 1:23:20 AM

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Alexandre Pierre, Flora Lemaire, Aïda Meghraoui-Kheddar, Sandra Audonnet, Stéphanie Héry-Huynh, et al.. Impact of aging on inflammatory and immune responses during elastin peptide-induced murine emphysema. American Journal of Physiology - Lung Cellular and Molecular Physiology, American Physiological Society, 2019, 316 (4), pp.L608-L620. ⟨10.1152/ajplung.00402.2018⟩. ⟨hal-02274365⟩

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