title: Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure.
abstract: Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. 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 α-2-macroglobulin, and α1-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 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 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, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA.
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shannahan
authors.forename: Oscar
authors.initials: O
authors.lastname: Alzate
authors.forename: Witold M
authors.initials: WM
authors.lastname: Winnik
authors.forename: Debora
authors.initials: D
authors.lastname: Andrews
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gavett
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced* / Q000276:immunology; D052242:Adiponectin / Q000097:blood; D000818:Animals; D017636:Asbestos, Amphibole / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D020738:Leptin / Q000097:blood; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008259:Macroglobulins / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000276:immunology; D009961:Orosomucoid / Q000378:metabolism; D053495:Osteopontin / Q000097:blood; D040901:Proteomics; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012189:Retrospective Studies
chemical_list: D052242:Adiponectin; D017636:Asbestos, Amphibole; D015415:Biomarkers; C097278:Lcn2 protein, rat; D020738:Leptin; D000071068:Lipocalin-2; D054834:Lipocalins; D008259:Macroglobulins; C506108:Orm1 protein, rat; D009961:Orosomucoid; C506897:Spp1 protein, rat; D053495:Osteopontin