Published ahead of print on December 20, 2007, doi:10.1165/rcmb.2007-0255OC Am. J. Respir. Cell Mol. Biol., Volume 38, Number 5, May 2008, 579-590 A more recent version of this article appeared on May 1, 2008
Submitted on July 3, 2007 Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and InfectivityAnna A Shvedova1*,1 Pathology/Physiology Research Branch, HELD, NIOSH, Morgantown, WV, USA, 2 Departments of Environmental and Occupational Health and Pharmacology, University of Pittsburgh, Graduate School of Public Health, Center for Free Radical and Antioxidant Health, Pittsburgh, PA, USA * To whom correspondence should be addressed. E-mail: ats1{at}cdc.gov.
Carbon nanotubes (CNT), with their applications in industry and medicine, may lead to new risks to human health. CNTs induce a robust pulmonary inflammation and oxidative stress in rodents. Realistic exposures to CNT may occur in conjunction with other pathogenic impacts (microbial infections) and trigger enhanced responses. We evaluated interactions between pharyngeal aspiration of single walled CNT (SWCNT) and bacterial pulmonary infection of C57BL/6 mice with Listeria monocytogenes (LM). Mice were given SWCNT (0, 10 and 40 µg/mouse) and 3 days later exposed to LM (103 bacteria/mouse). Sequential exposure to SWCNT/LM amplified lung inflammation and collagen formation. Despite this robust inflammatory response, SWCNT pre-exposure significantly decreased the pulmonary clearance of LM measured 3 - 7 days after microbial infection vs PBS/LM treated mice. Decreased bacterial clearance in SWCNT pre-exposed mice was associated with decreased phagocytosis of bacteria by macrophages and a decrease in nitric oxide production by these phagocytes. Pre-incubation of naive alveolar macrophages with SWCNT in vitro also resulted in decreased nitric oxide generation and suppressed phagocytizing activity towards LM. Failure of SWCNT-exposed mice to clear LM led to a continued elevation in nearly all major chemokines and acute phase cytokines into the later course of infection. In SWCNT/LM exposed mice, BAL PMNs, AMs and lymphocytes as well as LDH level were increased compared to mice exposed to SWCNT or LM alone. In conclusion, enhanced acute inflammation and pulmonary injury with delayed bacterial clearance after SWCNT exposure may lead to increased susceptibility to lung infection in exposed populations.
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