Differentiation of the roles of NO from airway epithelium and inflammatory cells in ozone-induced lung inflammation.

Toxicology and Applied Pharmacology
Nicholas J KenyonJerold A Last

Abstract

Mice lacking inducible nitric oxide synthase (NOS2-/-) are more susceptible to ozone-induced lung inflammation and injury than their isogenic wild-type (NOS2+/+) counterparts, demonstrating an apparent protective effect for NOS2 in murine lungs. We hypothesized that nitric oxide (NO) generated from either NOS2 in the airway epithelial cells or the bone-marrow-derived inflammatory cells was responsible for the protective effect of NOS2. To test this hypothesis, we prepared chimeric mice by killing their endogenous bone marrow cells by whole body irradiation followed by bone marrow transplantation from a heterologous donor mouse. We exposed C57BL/6 (NOS2+/+), NOS2-/-, and chimeric NOS2 mice (NOS2-/+, NOS2+/-) to 1 ppm of ozone for 3 consecutive nights. NOS2-/- mice were more severely injured after exposure to ozone than C57BL/6 mice, including a more robust inflammatory cell influx (4.14 x 10(5) +/- 2.19 x 10(5) vs. 2.78 x 10(5) +/- 1.36 x 10(5) cells respectively; P = 0.036) and greater oxidation of total protein sulfhydryls (R-SH) in their blood plasma. Chimeric NOS2-/+ mice, which had bone marrow from NOS2-/- mice transplanted into C57BL/6 recipients, had a significantly greater response to ozone (increased numbers of neutroph...Continue Reading

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Sep 27, 2005·Toxicology and Applied Pharmacology·Jerold A LastNicholas J Kenyon

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Citations

Oct 19, 2010·Mediators of Inflammation·Jennifer M BrattNicholas J Kenyon
Apr 4, 2008·Toxicology and Applied Pharmacology·Teresa C Wegesser, Jerold A Last
Sep 26, 2007·Clinical and Experimental Immunology·S MeyerB Beck-Schimmer
May 31, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samantha J SnowUrmila P Kodavanti
Sep 20, 2012·Journal of Breath Research·Nhât-Nam Le-DongAnh Tuan Dinh-Xuan
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gertrud U SchusterCharles B Stephensen

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