Differential contribution of bone marrow-derived infiltrating monocytes and resident macrophages to persistent lung inflammation in chronic air pollution exposure
SCIENTIFIC REPORTS(2020)
摘要
Chronic exposure to particulate matter < 2.5µ (PM 2.5 ) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (A Φ ) are long-lived, self-renew and critical to the health impact of inhalational insults. There is an inadequate understanding of the impact of PM 2.5 exposure on the nature/time course of transcriptional responses, self-renewal of A Φ , and the contribution from bone marrow (BM) to this population. Accordingly, we exposed chimeric (CD45.2/CD45.1) mice to concentrated PM 2.5 or filtered air (FA) to evaluate the impact on these end-points. PM 2.5 exposure for 4-weeks induced an influx of BM-derived monocytes into the lungs with no contribution to the overall TR-A Φ pool. Chronic (32-weeks) PM 2.5 exposure on the other hand while associated with increased recruitment of BM-derived monocytes and their incorporation into the A Φ population, resulted in enhanced apoptosis and decreased proliferation of TR-A Φ . RNA-seq analysis of isolated TR-A Φ and BM-A Φ from 4- and 32-weeks exposed mice revealed a unique time-dependent pattern of differentially expressed genes. PM 2.5 exposure resulted in altered histological changes in the lungs, a reduced alveolar fraction which corresponded to protracted lung inflammation. Our findings suggest a time-dependent entrainment of BM-derived monocytes into the A Φ population of PM 2.5 exposed mice, that together with enhanced apoptosis of TR-A Φ and reorganization of transcriptional responses, could collectively contribute to the perpetuation of chronic inflammation.
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关键词
Alveolar macrophages,Environmental impact,Immunology,Inflammation,Science,Humanities and Social Sciences,multidisciplinary
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