PGE2accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking
Year: 2020
Type: article
Abstract: Alveolar macrophages (AMs) are resident immune cells of the lung that are critical for host defense. AMs are capable of proliferative renewal, yet their numbers are known to decrease with aging and increase with cigarette smoking. The mechanism by which AM proliferation is physiologically restrained, and whether dysregulation of this brake contributes to altered AM numbers in pathologic circumstances, however, remains unknown. Mice of advanced age exhibited diminished basal AM numbers and contained elevated PGE2levels in their bronchoalveolar lavage fluid (BALF) as compared with young mice. Exogenous PGE2inhibited AM proliferation in an E prostanoid receptor 2 (EP2)-cyclic AMP-dependent manner. Furthermore, EP2 knockout (EP2 KO) mice exhibited elevated basal AM numbers, and their AMs resisted the ability of PGE2and aged BALF to inhibit proliferation. In contrast, increased numbers of AMs in mice exposed to cigarette smoking were associated with reduced PGE2levels in BALF and were further exaggerated in EP2 KO mice. Collectively, our findings demonstrate that PGE2functions as a tunable brake on AM numbers under physiologic and pathophysiological conditions.
Source: Life Science Alliance
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: American Cancer Society, U.S. Department of Veterans Affairs, Flight Attendant Medical Research Institute, National Institutes of Health, Michigan Institute for Clinical and Health Research, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: Research Training in Experimental Immunology, G109073144, G1237957884, G1286755950, G1331737163, Transforming Translational Science and Education to Benefit Human Health, G2331765193, G2626767253, Understanding the Lung Microbiome in HIV-Infected and HIV-uninfected individuals, Academic leadership in the Biology of Aging and Cardiovascular Diseases, G3207190415, G343592946, Mechanisms of dysregulated immunity with aging, G6045082340, G6060984277, Secreted SOCS Proteins as Vectors of Lung Macrophage to Epithelial Cell Crosstalk, G7201975796, Novel mechanisms of age-enhanced vasculopathy after heart transplantation, G7916689590, Claude D. Pepper Older Americans Independence Center at the University of Michigan (UM Pepper Center), Novel Functions of Lung Macrophages and Fibroblasts in Pulmonary Inflammation and Fibrosis, Multidisciplinary Training Program in Lung Disease
OpenAlex ID: W3081244137