Advanced in vitro exposure systems.

Effects of acute in vitro exposure of murine precision-cut lung slices to gaseous nitrogen dioxide and ozone in an air-liquid interface (ALI) culture

30. Jun. 2010

Toxicology Letters

2010 Jul 1;196(2):117-24. doi: 10.1016/j.toxlet.2010.04.004. [epub ahead of print]

Authors
S. Switalla, J. Knebel, D. Ritter, N. Krug, A. Braun, K. Sewald∗

Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany

 

The publications shows a direct exposure to O(3) and NO(2) induced cytotoxicity and pro-inflammatory responses in precision-cut lung slices in an air-liquid interface culture. This provides a model that more closely resembles in vivo exposure of airborne contaminants.

Abstract

The aim of this study was to establish an air-liquid interface (ALI) culture of precision-cut lung slices (PCLS) for direct exposure of lung cells to gaseous contaminants. Nitrogen dioxide (NO(2)) and ozone (O(3)) were selected as model gas compounds. Acute pro-inflammatory and toxic effects of NO(2) and O(3) on live lung tissue were investigated. Murine PCLS were exposed to different flow rates (3-30mL/min) of synthetic air, O(3) (3.5-8.5ppm), or NO(2) (1-80ppm). Tissue survived ex vivo in ALI culture and resisted exposure to NO(2) (1-10ppm) and O(3) (3.5-8.5ppm) for 1h. Longer exposure to NO(2) resulted in a clear loss of viability, whereas exposure to O(3) was less effective. Exposure to NO(2) dose-dependently induced release of the pro-inflammatory IL-1alpha (40%), whereas RANTES, IL-12, and eotaxin remained unchanged. Early secretion of IL-1alpha (80%), RANTES (>800%), MIP-1beta (44%), and MCP-1 (60%) was already detected after 1h of exposure to O(3). The obtained data showed that direct exposure to O(3) and NO(2) induced cytotoxicity and pro-inflammatory responses in PCLS with ALI culture. This provides a model that more closely resembles in vivo exposure of airborne contaminants, and thus should be appropriate for toxicity testing.

PMID: 20394810 [PubMed - indexed for MEDLINE]

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