title: Exposure to a Mycobacterial Antigen, ESAT-6, Exacerbates Granulomatous and Fibrotic Changes in a Multiwall Carbon Nanotube Model of Chronic Pulmonary Disease.
abstract: Recent studies suggest additive effects of environmental pollutants and microbial antigens on respiratory disease. We established a granuloma model in which instilled multiwall carbon nanotubes (MWCNT) elicit granulomatous pathology. We hypothesized that mycobacterial antigen ESAT-6, a T cell activator associated with tuberculosis and sarcoidosis, might alter pathology. Wild-type C57Bl/6 mice received MWCNT with or without ESAT-6 peptide. Controls received vehicle (surfactant-PBS) or ESAT-6 alone. Mice were evaluated 60 days later for granulomas, fibrosis, and bronchoalveolar lavage (BAL) cell expression of inflammatory mediators (CCL2, MMP-12, and Osteopontin). Results indicated increased granulomas, fibrosis, and inflammatory mediators in mice receiving the combination of MWCNT+ESAT-6 compared to MWCNT or vehicle alone. ESAT-6 alone showed no significant effect on these pathological endpoints. However, CD3 (+) lymphocyte infiltration of lung tissue increased with MWCNT+ESAT-6 versus MWCNT alone. Findings suggest that concurrent exposure to microbial antigen and MWCNT exacerbates chronic pulmonary disease.
authors.forename: Anagha
authors.initials: A
authors.lastname: Malur
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Barna
authors.forename: Janki
authors.initials: J
authors.lastname: Patel
authors.forename: Matthew
authors.initials: M
authors.lastname: McPeek
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wingard
authors.forename: Larry
authors.initials: L
authors.lastname: Dobbs
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Thomassen
keywords: Carbon nanotube; Fibrosis; Granuloma; Mycobacterial antigen