PMID- 20394810 OWN - NLM STAT- MEDLINE DCOM- 20100527 LR - 20181121 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 196 IP - 2 DP - 2010 Jul 1 TI - 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. PG - 117-24 LID - 10.1016/j.toxlet.2010.04.004 [doi] AB - 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. FAU - Switalla, S AU - Switalla S AD - Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. FAU - Knebel, J AU - Knebel J FAU - Ritter, D AU - Ritter D FAU - Krug, N AU - Krug N FAU - Braun, A AU - Braun A FAU - Sewald, K AU - Sewald K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100413 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccl4 protein, mouse) RN - 0 (Ccl5 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Chemokine CCL5) RN - 0 (Gases) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1alpha) RN - 0 (Lipopolysaccharides) RN - 0 (lipopolysaccharide, Escherichia coli O111 B4) RN - 187348-17-0 (Interleukin-12) RN - 66H7ZZK23N (Ozone) RN - S7G510RUBH (Nitrogen Dioxide) SB - IM MH - Animals MH - Chemokine CCL2/metabolism MH - Chemokine CCL4/metabolism MH - Chemokine CCL5/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Gases MH - Inflammation Mediators/metabolism MH - Interleukin-12/metabolism MH - Interleukin-1alpha/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung/*drug effects/immunology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Nitrogen Dioxide/*toxicity MH - Ozone/*toxicity MH - Time Factors MH - Tissue Culture Techniques MH - Tissue Survival/drug effects EDAT- 2010/04/17 06:00 MHDA- 2010/05/28 06:00 CRDT- 2010/04/17 06:00 PHST- 2010/01/01 00:00 [received] PHST- 2010/03/12 00:00 [revised] PHST- 2010/04/07 00:00 [accepted] PHST- 2010/04/17 06:00 [entrez] PHST- 2010/04/17 06:00 [pubmed] PHST- 2010/05/28 06:00 [medline] AID - S0378-4274(10)01309-3 [pii] AID - 10.1016/j.toxlet.2010.04.004 [doi] PST - ppublish SO - Toxicol Lett. 2010 Jul 1;196(2):117-24. doi: 10.1016/j.toxlet.2010.04.004. Epub 2010 Apr 13.