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 (CdCl2) at 25, 100, or 400 micrograms/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 CdCl2 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 CdCl2 treatment. All doses of CdCl2 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 CdCl2 dose levels. The association of CdCl2-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.
Driscoll
K E
KE
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239.
Maurer
J K
JK
Poynter
J
J
Higgins
J
J
Asquith
T
T
Miller
N S
NS
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D019256:Cadmium Chloride; D002452:Cell Count / Q000187:drug effects; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism*; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002712:Chlorides; D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium; D019256:Cadmium Chloride; D006909:Hydroxyproline