Differential contribution of bone marrow-derived infiltrating monocytes and resident macrophages to persistent lung inflammation in chronic air pollution exposure.
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ABSTRACT:
SUBMITTER: Gangwar RS
PROVIDER: S-EPMC7462977 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Differential contribution of bone marrow-derived infiltrating monocytes and resident macrophages to persistent lung inflammation in chronic air pollution exposure.
Gangwar Roopesh Singh RS Vinayachandran Vinesh V Rengasamy Palanivel P Chan Ricky R Park Bongsoo B Diamond-Zaluski Rachel R Cara Elaine Ann EA Cha Anthony A Das Lopa L Asase Courteney C Maiseyeu Andrei A Deiuliis Jeffrey J Zhong Jixin J Mitzner Wayne W Biswal Shyam S Rajagopalan Sanjay S
Scientific reports 20200901 1
Chronic exposure to particulate matter < 2.5µ (PM<sub>2.5</sub>) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (AΦ) are long-lived, self-renew and critical to the health impact of inhalational insults. There is an inadequate understanding of the impact of PM<sub>2.5</sub> exposure on the nature/time course of transcriptional responses, self-renewal of AΦ, and the contribution from bone marrow (BM) to this population. Accordingly, we exposed chimeric (CD45. ...[more]
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Project description:Chronic exposure to ambient particulate matter <2.5µ (PM2.5) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (AΦ) are long lived, self-renew and critical to the health impact of inhalational insults. There is inadequate understanding of the impact of PM2.5 exposure on nature/time course of transcriptional responses and the proliferation/maintenance of AΦ including the contribution from bone marrow (BM) over chronic time periods. We investigated the effects of exposure to real-world concentrated PM2.5 or filtered air (FA) in chimeric (CD45.2/CD45.1) mice. Here, we show that PM2.5 exposure induces an influx of BM-derived monocytes to lungs at 4-weeks, with no contribution to TR-AΦ population. Chronic (32-weeks) PM2.5 exposure resulted in enhanced apoptosis (Annexin V+) and decreased proliferation (BrdU+) of TR-AΦ and presence of BM-AΦ in inflamed lungs. RNA-seq analysis of flow sorted TR-AΦ and BM-AΦ from 4 and 32-weeks exposed mice, revealed a unique time dependent pattern of differentially expressed genes, with PM2.5 exposure with a pro-inflammatory bias. PM2.5 exposure resulted in pulmonary fibrosis and reduced alveolar fraction which corresponded to protracted lung inflammation. Our findings suggest a time dependent PM2.5 entrainment of a BM-derived monocytes infiltration into PM2.5 exposed lungs with an inflammatory phenotype, that together with enhanced apoptosis of TR-AΦ and pro-inflammatory polarization may contribute to perpetuation of chronic inflammation and lung fibrosis.
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