Abstract: Slide Presentations |


Monisha Das, MD*; Tim Quinn; Masha Nzabi, MD; Betty Herndon, PhD
Author and Funding Information

University of Missouri Kansas City school of Medicine, Kansas City, MO


Chest. 2009;136(4_MeetingAbstracts):48S. doi:10.1378/chest.136.4_MeetingAbstracts.48S-f
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PURPOSE:  Carbon-based nanoparticles are used in drug delivery, consumer products and electronic manufacture. Since a major route of exposure is by inhalation, it was important to evaluate pulmonary effects. We have observed rapid tissue eosinophilia following intratracheal (i.t) carbon nanotube (CNT) animal dosage. This study investigates mechanisms of that phenomenon. It is known that cell injury releases damage associated molecular pathway molecules, one of which includes the high mobility group box protein 1, (HMGB1), which activates the innate immune system. We hypothesized that HMGB1, released from CNT-damaged cells, leads to the observed tissue inflammation.

METHODS:  Following IACUC approval, Sprague Dawley rats received 50αL lung surfactant containing 500αg CNT intratracheal. At necropsy (30 minutes, 3 hours, 24 hours, 1 week, and 2 weeks) pleural fluid, bronchoalveolar lavage (BAL) and sera were collected for cell counts, and HMGB1 ELISA. Lungs were fixed and immunostained with anti-HMGB1. Data were analyzed by ANOVA and post-tests.

RESULTS:  HMGB1 was elevated in BAL (106.2 ng/mg protein at 30 min, 43.5 at 3hr to 214.7 at 2weeks) after i.t. nanoparticles (p=0.02, 3hr and p=0.048, 24hr vs control and 2 week counts. Eosinophils and in tissue and pleural fluid were elevated early (0.5hr –3days) and significantly over controls. Macrophages in tissue followed the HMGB1 pattern.

CONCLUSION:  Nanoparticles produce a sterile alarm response in rat lung reflected by immediate eosinophilia, HMGB1 and receptor release and activation that continues over 2 weeks following a single 500 microgram, 50 microliter i.t. dose. Cellular necrosis is also seen.

CLINICAL IMPLICATIONS:  Based on the pulmonary effects of nanoparticles and the potential for greater exposure with their increasing use, the present topic is of interest to all of pulmonary medicine. The observed alarm response may be the first sign of unsuspected pulmonary cellular sequela.

DISCLOSURE:  Monisha Das, No Financial Disclosure Information; No Product/Research Disclosure Information

Wednesday, November 4, 2009

10:30 AM - 12:00 PM




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