title: Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.
abstract: Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710-0001, USA. white141@mc.duke.edu
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Whitehead
authors.forename: Keith A
authors.initials: KA
authors.lastname: Grasman
authors.forename: Edgar C
authors.initials: EC
authors.lastname: Kimmel
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D004852:Epoxy Compounds / Q000633:toxicity*; D006108:Graphite / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D015846:Monokines / Q000096:biosynthesis; D010269:Paraquat / Q000633:toxicity; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012906:Smoke / Q000009:adverse effects; D015208:Smoke Inhalation Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D054426:Chemokine CXCL2; D004852:Epoxy Compounds; D006540:Herbicides; D015846:Monokines; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D006108:Graphite; D007371:Interferon-gamma; D010269:Paraquat