Lung inflammation and thrombogenic responses in a time course study of Csb mice exposed to ozone

Abstract

Ozone is a well-known oxidant air pollutant, inhalation of which can result in oxidative stress, and lead to pulmonary inflammation. The aim of this study was to evaluate the time-course events after a single ozone exposure in transcription-coupled repair defective Csb and wild type mice. Mice were exposed for 3 h to 2 ppm ozone and biological parameters related to oxidative stress and inflammation were examined in the lungs at 0, 4, 9, 24 and 48 h after exposure. In addition the procoagulant and thrombomodulin activities were explored by a combination of assays for tissue factor and thrombin generation. This study revealed a significant biological response to ozone, for both Csb and wild type mice. The onset of inflammation in Csb mice, as indicated by an increase in interleukin-6, tumor necrosis factor-alpha and total cell influx, occurred earlier compared with those seen in wild type mice. On the other hand, Csb mice showed a delayed antioxidant reaction compared with wild type mice. Both genotypes developed a procoagulant reaction characterized by a stably increased tissue factor activity and a progressive increase in thrombin generation after 2 days. These experiments have shown that ozone, a well-known toxic substance from the environment, induces not only inflammation, but also procoagulant reactions in the lungs of mice. These results have implications for understanding the systemic effects induced by oxidant air pollutants.

The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children

“…Furthermore, it is documented that a single O 3 exposure might induce significant biological response in TM level, inflammatory and pro-coagulant reactions in the lungs of mice [18]. Consistent with this study, we found that O 3 level was significantly associated with TF and TM.…”

“…Findings of experimental studies suggest that exposure to air pollution may result in increase in TF and decrease in TM [18,19]. …”

Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

“…Overall, these studies show that genes related to innate immune signaling—in particular TNF receptors 1/2 and toll-like receptors 2/4—may modulate risk related to O 3 exposure, as well as associated genes including Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1), Jnk1 (mitogen-activated protein kinase 8; Mapk8 ), Cd44 (Cd44 antigen), Myd88 (myeloid differentiation primary response gene 88), Iai (inter-α-trypsin inhibitor), Hsp70 (heat shock protein 70), Mmp9 (matrix metallopeptidase 9), and Nos2 (nitric oxide synthase 2, inducible) (Bauer et al 2011; Cho et al 2001, 2007; Fakhrzadeh et al 2002; Garantziotis et al 2009; Hollingsworth et al 2004; Kenyon et al 2002; Kleeberger et al 2000, 2001; Williams et al 2007; Yoon et al 2007). There is also toxicologic evidence indicating that genes involved in pro- and anti-inflammatory signaling and oxidative stress modulate the O 3 response, including interleukins Il10 , Il13 , and Il6 , and Cxcr2 [chemokine (C-X-C motif) receptor 2], Marco (macrophage receptor with collagenous structure), Csb (excision repair cross-complementation group 6), and Nqo1 (Backus et al 2010; Dahl et al 2007; Johnston et al 2005a, 2005b; Kooter et al 2008; Voynow et al 2009; Williams et al 2008). Taken together, this evidence suggests the complexity of the biological mechanisms underlying airway inflammation and airway hyperresponsiveness (AHR) as well as genetic susceptibility, as previously described by Bauer and Kleeberger (2010).…”

Diesel Engine Exhaust Initiates a Sequence of Pulmonary and Cardiovascular Effects in Rats

“…First of all, a procoagulant effect was observed in lung tissue as indicated by increased TF activity and thrombin generation upon DEE exposure. Increased thrombin generation is most likely the resultant of increased TF and decreased thrombomodulin expression, due to inflammatory stimulation [33]. Second, the overall plasma haemostatic balance was shifted towards a procoagulant state.…”