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Phenotypic Switching of Macrophages in response to EPFRs
Author(s) -
Raman Girija,
Mahne Sarah,
Varner Kurt J
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.811.2
Combustion generated environmentally persistent free radicals (EPFR) contribute to adverse health effects of inhaled particulate matter. When exposed to EPFR's at different concentration levels monocytes/macrophages experience varied microenvironments that alter their phenotype and biological function. The goal of the study was to explore the phenotypic changes in macrophages elicited by EPFR's. The particles used were composed of the EPFR of 1,2‐dichlorobenzene formed by the thermal reaction with Si particles containing (200 nm) 3% CuO (DCB230). Treatment of RAW 264.7 cells with DCB‐230 (1 – 20 μg/ cm 3 ) caused a dose‐related phenotypic switch from predominantly arginase‐2 positive macrophages to the inflammatory iNOS2 positive phenotype. The dose‐related increases in Nrf2 and heme oxygenase‐1(HO‐1) observed in RAW 264.7 by DCB230, suggest that oxidative stress underlies the phenotypic switch. Macrophages isolated from the peripheral blood of rats treated with DCB‐230 exhibit a predominantly CD163/arginase‐2 positive phenotype. Infiltration of arginase‐2 positive and HO‐1 positive macrophages was also observed in the left ventricle of treated rats. This phenotypic differentiation of macrophages after exposure to DCB230 is determined by the relative level of oxidative stress produced by EPFRs. Supported NIH P20ES013648