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Release of ECSOD from alveolar macrophages in response to asbestos fibers correlates with decreased TNFα production and induction of apoptosis
Author(s) -
Fattman Cheryl L.,
Argoti Pedro S.,
Torres German M.,
Oury Tim D.,
Ortiz Luis A.
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.21.6.a821
Asbestosis is a chronic disease with a dismal prognosis. Phagocytosis of asbestos fibers by macrophages mediates fibrotic disease development. Phagocytosis results in the production and release of reactive oxygen species and TNFα, both of which impact macrophage viability. The antioxidant enzyme ECSOD scavenges superoxide anions, producing H 2 O 2 as a byproduct. ECSOD is highly expressed in lung macrophages and accumulates in the airspaces of asbestos‐injured lungs. Interestingly, a recent study showed that elevated concentrations H 2 O 2 of modulate TNFα gene expression. We hypothesize that macrophage survival is influenced by TNFα production in response to elevated levels of H 2 O 2 generated by ECSOD. Treatment of RAW 267.4 macrophages with asbestos results in enhanced TNFα production. In contrast, IC‐21 macrophages do not produce TNFα in response to fibers. In addition, asbestos‐treated IC‐21 cells exhibit increased caspase activity as compared to RAW 267.4 cells. Unstimulated cells express ECSOD. However, upon stimulation, IC‐21 cells release more ECSOD into the surrounding media than RAW 267.4 cells. Conversely, stimulated RAW 267.4 cells contain more intracellular ECSOD. These results suggest that intra celluar ECSOD may provide protection to macrophages (either directly as an antioxidant or indirectly through TNFα production) and that this protection is lost when ECSOD is released from the cells.