Abstract
Cigarette smoke (CS) is the major cause of chronic lung injuries, such as chronic obstructive pulmonary disease (COPD). In patients with severe COPD, tertiary lymphoid follicles containing B lymphocytes and B cell-activating factor (BAFF) overexpression are associated with disease severity. In addition, BAFF promotes adaptive immunity in smokers and mice chronically exposed to CS. However, the role of BAFF in the early phase of innate immunity has never been investigated. We acutely exposed C57BL/6J mice to CS and show early BAFF expression in the bronchoalveolar space and lung tissue that correlates to airway neutrophil and macrophage influx. Immunostaining analysis revealed that neutrophils are the major source of BAFF. We confirmed in vitro that neutrophils secrete BAFF in response to cigarette smoke extract (CSE) stimulation. Antibody-mediated neutrophil depletion significantly dampens lung inflammation to CS exposure but only partially decreases BAFF expression in lung tissue and bronchoalveolar space suggesting additional sources of BAFF. Importantly, BAFF deficient mice displayed decreased airway neutrophil recruiting chemokines and neutrophil influx while the addition of exogenous BAFF significantly enhanced this CS-induced neutrophilic inflammation. This demonstrates that BAFF is a key proinflammatory cytokine and that innate immune cells in particular neutrophils, are an unconsidered source of BAFF in early stages of CS-induced innate immunity.
Highlights
Inflammatory lung diseases represent a major public health problem
wild type mice (WT) mice exposed to cigarette smoke (CS) presented significant increase in the number of total cells recruited into the bronchoalveolar lavage (BAL) (Figure 1A) and in particular neutrophils (Figure 1B) and macrophages (Figure 1C), as well as enhanced myeloperoxidase (MPO) levels (Figure 1D) in BAL fluid (BALF) which correlates with neutrophil recruitment
BAL cells immunostaining assay employing B cell activating factor (BAFF) specific antibody indicates that airways recruited neutrophils, identified by their multi-lobulated nucleus stained with DAPI, strongly express BAFF in response to CS (Figures 1H,I)
Summary
Inflammatory lung diseases represent a major public health problem Their incidence is constantly increasing and the predictions of the World Health Organization (WHO) are at least pessimistic over the 20–30 years, reflecting recent changes in our society and the associated consequences on air quality and social behavior. A sustained cellular inflammation characterized by airway neutrophilic recruitment is commonly correlated with bad prognosis in chronic lung inflammation and COPD exacerbations elicited by a bacterial or viral infection [2]. This strong inflammatory response is associated with impaired bacterial clearance due to ineffective neutrophils which do not prevent the occurrence of infection-driven exacerbations [1]. The transition between proinflammatory and immunosuppressive neutrophils is highly dynamic and neutrophil plasticity may influence immune responses to environmental stress such as CS exposure [6]
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