Abstract
Chronic exposure to 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 an inadequate understanding of the impact of PM2.5 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 (CD45.2/CD45.1) mice to concentrated PM2.5 or filtered air (FA) to evaluate the impact on these end-points. PM2.5 exposure for 4-weeks induced an influx of BM-derived monocytes into the lungs with no contribution to the overall TR-AΦ pool. Chronic (32-weeks) PM2.5 exposure on the other hand while associated with increased recruitment of BM-derived monocytes and their incorporation into the AΦ population, resulted in enhanced apoptosis and decreased proliferation of TR-AΦ. RNA-seq analysis of isolated TR-AΦ and BM-AΦ from 4- and 32-weeks exposed mice revealed a unique time-dependent pattern of differentially expressed genes. PM2.5 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 AΦ population of PM2.5 exposed mice, that together with enhanced apoptosis of TR-AΦ and reorganization of transcriptional responses, could collectively contribute to the perpetuation of chronic inflammation.
Highlights
Chronic exposure to particulate matter < 2.5μ (PM2.5) has been linked to cardiopulmonary disease
Short‐term (4‐week) PM2.5 exposure induces recruitment of bone marrow‐derived monocytes into lung without evidence of differentiation into alveolar macrophages
Chest shielding preserved the lungs from irradiation and thereby allowing all tissue-resident AΦ and myeloid cells in the lungs to remain as CD45.2 origin, while peripheral blood myeloid cells were replaced by CD45.1 bone marrow
Summary
Chronic exposure to particulate matter < 2.5μ (PM2.5) has been linked to cardiopulmonary disease. There is an inadequate understanding of the impact of PM2.5 exposure on the nature/time course of transcriptional responses, self-renewal of AΦ, and the contribution from bone marrow (BM) to this population. Chronic (32-weeks) PM2.5 exposure on the other hand while associated with increased recruitment of BM-derived monocytes and their incorporation into the AΦ population, resulted in enhanced apoptosis and decreased proliferation of TR-AΦ. Our findings suggest a time-dependent entrainment of BM-derived monocytes into the AΦ population of PM2.5 exposed mice, that together with enhanced apoptosis of TR-AΦ and reorganization of transcriptional responses, could collectively contribute to the perpetuation of chronic inflammation. AΦ of the lung are long-lived and self-renew to maintain their population without contribution from circulating adult bone marrow-derived m onocytes[5,6]. We posit that a better understanding of the lung immune response with chronic inhalation to air pollution across the life span may provide much-needed insights into the chronic biology of an omnipresent risk factor
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