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Persistent inflammation and the generation of reactive oxygen and nitrogen species play pivotal roles in tissue injury during disease pathogenesis and as a reaction to toxicant exposures. The associated oxidative and nitrative stress promote diverse pathologic reactions including neurodegenerative disorders, atherosclerosis, chronic inflammation, cancer,(More)
Nitric oxide is a highly reactive molecule that has been implicated in host defense and in tissue injury. In the present studies we analyzed the effects of brief exposure of rats to inhaled ozone on production of this mediator by lung macrophages and type II epithelial cells. We found that ozone exposure (1-2 ppm, 3 hr) induced a marked increase in(More)
Interleukin-1 (IL-1) and interleukin-6 (IL-6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL-1 and IL-6, suggesting that these cells also participate in these processes. Endothelial cells and macrophages(More)
Although initially considered merely "scavenger cells" that participate in immunologic responses only after B and T lymphocytes have performed their biological tasks, more recent evidence suggests that macrophages play a key role in host defense as well as in the maintenance of normal tissue structure and function. For macrophages to perform their(More)
Nitric oxide is a short-lived cytotoxic mediator that has been implicated in the pathogenesis of endotoxin-induced tissue injury and septic shock. In the present studies we determined whether this mediator is produced in the lung during acute endotoxemia. We found that intravenous injection of rats with bacterially derived lipopolysaccharide (LPS), a(More)
Alert me to new issues of the journal Download to citation manager FORMER CALIFORNIA GOVERNOR Jerry Brown advocated the mantra that "small is beautiful." The paper by Shvedova et al., the current article in focus (Ref. 15, see p. L698 in this issue), suggests some less-attractive perspectives of this vision. Nanomaterials are receiving increasing attention(More)
Reactive oxygen intermediates have been implicated in lung injury induced by inhaled irritants. The present studies used mice overexpressing Cu/Zn-superoxide dismutase (SODϩ/ϩ) to analyze their role in ozone-induced lung inflammation and cytotoxicity. Treatment of wild-type mice with ozone (0.8 ppm, 3 h) resulted in increased bronchoalveolar lavage fluid(More)
Inhaled nitric oxide is a selective pulmonary vasodilator used for the treatment of pulmonary hypertension. The potential adverse effects of inhaled nitric oxide are unknown and represent the focus of the present studies. Whereas inhalation of nitric oxide (10 to 100 ppm, 5 h) by Balb/c mice had no effect on the number or type of cells recovered from the(More)
Ozone-induced lung injury is associated with increased production of reactive nitrogen intermediates and TNF-α which have been implicated in the pathogenic process. The generation of these mediators is regulated in part by transcription factors such as NF-κB and C/EBP. The present studies used NF-κB p50 knockout mice to assess the role of this transcription(More)
Lipopolysaccharide (LPS) is a toxic bacterial cell wall component that is rapidly cleared from the portal circulation by Kupffer cells. To determine if interaction with LPS causes the accumulation and activation of mononuclear phagocytes (MNP) in the liver, we compared the morphological and functional characteristics of MNP obtained from livers of rats(More)