PLX180933

GSE143787: Differential contribution of bone marrow derived-monocytes to the lung tissue resident alveolar macrophages and persistent lung inflammation with chronic air pollution exposure

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Chronic exposure to ambient particulate matter <2.5 (PM2.5) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (A) 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 A 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-A population. Chronic (32-weeks) PM2.5 exposure resulted in enhanced apoptosis (Annexin V+) and decreased proliferation (BrdU+) of TR-A and presence of BM-A in inflamed lungs. RNA-seq analysis of flow sorted TR-A and BM-A 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-A and pro-inflammatory polarization may contribute to perpetuation of chronic inflammation and lung fibrosis. SOURCE: Ernest,R,Chan (erc6@case.edu) - CWRU