Differential contribution of bone marrow-derived infiltrating monocytes and resident macrophages to persistent lung inflammation in chronic air pollution exposure
Roopesh Singh Gangwar, Vinesh Vinayachandran, Rengasamy Palanivel, Ricky Chan, Bongsoo Park, Rachel Diamond‐Zaluski, Elaine Ann Cara, Anthony Cha, Lopa Das, Courteney Asase, Andrei Maiseyeu, Jeffrey A. Deiuliis, Jixin Zhong, Wayne Mitzner, Shyam Biswal, Sanjay Rajagopalan
Abstract
Abstract 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.