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Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure
Shannahan, J., O. Alzate, W. M. WINNIK, D. L. ANDREWS, M. SCHLADWEILER, A. J. GHIO, S. H. GAVETT, AND U. P. KODAVANTI. Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 260(2):105-14, (2012).
Background: Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. Objective: We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. Methods and Results: In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in alpha-2-macroglobulin, and n l-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain-and age-related changes were apparent in MetS biomarkers no LA effects were evident. The cancer marker mesothelin was increased only slightly at I-month in WKY. Quantitative Intact Proteomic profiling of WKY serum at I-day or 4-weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, a-2-HSglycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, and serum amyloid P, and more I-day after last LA exposure. All changes were reversible after a short recovery regardless ofthe acute or long-term exposures. Conclusion: LA induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA.
We demonstrate that for the first time that as with other air pollutant acute exposure to Libby asbestos increases circulating protein biomarkers associated with acute phase response. Novel inflammatory biomarkers such as lipocalin-2 and osteopontin but not classical markers such as IL-6 and TNF-a are increased in the serum. These novel findings have implications on the field of biomarkers. These data support the recent epidemiology of Libby region showing association between Libby amphibole exposure and increases in mortality due to cardiovascular cause
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH