Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis

Rats were exposed to saline or cadmium chloride (CdCl 2) at 25, 100, or 400 μg/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydr...

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Veröffentlicht in:Toxicology and applied pharmacology 1992-09, Vol.116 (1), p.30-37
Hauptverfasser: Driscoll, Kevin E., Maurer, James K., Poynter, James, Higgins, Janet, Asquith, Thomas, Miller, Nita Sue
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container_issue 1
container_start_page 30
container_title Toxicology and applied pharmacology
container_volume 116
creator Driscoll, Kevin E.
Maurer, James K.
Poynter, James
Higgins, Janet
Asquith, Thomas
Miller, Nita Sue
description Rats were exposed to saline or cadmium chloride (CdCl 2) at 25, 100, or 400 μg/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl 2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl 2 treatment. All doses of CdCl 2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl 2 dose levels. The association of CdCl 2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.
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At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl 2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl 2 treatment. All doses of CdCl 2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl 2 dose levels. 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At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl 2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl 2 treatment. All doses of CdCl 2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl 2 dose levels. The association of CdCl 2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>1529450</pmid><doi>10.1016/0041-008X(92)90141-E</doi><tpages>8</tpages></addata></record>
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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Biological and medical sciences
Bronchoalveolar Lavage Fluid - cytology
Cadmium - administration & dosage
Cadmium - toxicity
Cadmium Chloride
Cell Count - drug effects
Chlorides - administration & dosage
Chlorides - toxicity
Disease Models, Animal
Fibronectins - metabolism
Hydroxyproline - analysis
Lung - chemistry
Lung - drug effects
Lung - pathology
Macrophages, Alveolar - drug effects
Macrophages, Alveolar - metabolism
Male
Medical sciences
Pneumology
Pulmonary Fibrosis - chemically induced
Rats
Rats, Inbred F344
Respiratory system : syndromes and miscellaneous diseases
Tumor Necrosis Factor-alpha - metabolism
title Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis
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