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MATRILYSIN PARTICIPATES IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PRODUCTS
Citation:
Dreher, K L., W. Y. Su, AND C. L. Wilson. MATRILYSIN PARTICIPATES IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PRODUCTS. Presented at SOT, San Francisco, CA, March 25-29, 2001.
Description:
ROLE OF MATRILYSIN IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PARTICLES.
K L Dreher1, WY Su2 and C L Wilson3. 1US Environmental Protection Agency, Research Triangle Park, NC; 2Duke University, Durham, NC;3Washington University, St. Louis, MO.
Mechanisms by which combustion particles and ambient air particulate matter (PM) mediate their adverse health effects remains a critical uncertainty in ambient air PM health risk assessment. Matrix metalloproteinases (MMPs) normally function in wound repair but have been implicated in the pathogenesis of a variety of lung diseases such as idiopathic fibrosis, emphysema, and asthma. Residual oil fly ash (ROFA) and ambient air PM have been shown to induce pulmonary gene and protein expression of various MMPs (Am. J. Physiol. Lung Cell Mol. Physiol. 279:L152-L160, 2000; Inhal. Toxicol. 12 (Suppl. 2) 105-119, 2000). However, the roles which MMPs play in ROFA and ambient air PM-induced lung injury are unknown. This study examines the role which matrilysin (MMP-7) plays in ROFA-induced acute lung injury. MMP-7 knockout (MMP-7 -/-) and wildtype (MMP-7 +/+) mice were exposed to ROFA by intratracheal instillation (dose: 50 g ROFA/mouse). Bronchoalveolar lavage fluid (BALF) samples were recovered from mice at 6h and 24h post-exposure and examined for biomarkers of lung injury. No differences in pulmonary edema, cytotoxicity or inflammation were observed between MMP-7 -/- and MMP-7 +/+ mice at 6h post-exposure. However, at 24h post-ROFA exposure modest but significant decreases in BALF biomarkers of pulmonary edema and cytotoxicity (25% decrease in protein/ml, 28% decrease in albumin/ml, and 20% decrease in lactate dehydrogenase U/l) were observed in MMP-7 -/- when compared to ROFA exposed MMP-7 +/+ mice. Dramatic decreases in BALF biomarkers of cellular inflammation (38% decrease in cells/ml; 51% decrease in neutrophil/ml; and 78% decrease in eosinophil/ml) were observed in ROFA exposed MMP-7 -/- mice when compared to similarly treated MMP-7 +/+ mice at 24h post-exposure. These results demonstrate that matrilysin plays a significant role in ROFA-induced acute lung injury.(This abstract does not reflect EPA policy)
Submitted to 2001 The Society of Toxicology Meeting