Patterns of secretion of transforming growth factor-alpha (TGF-alpha) in experimental silicosis. Acute and subacute effects of cristobalite exposure in the rat.
Transforming growth factor-alpha (TGF-alpha) a cytokine having potent mitogenic activity for epithelial and mesenchymal cells, may play a role in the lung remodeling of silicosis. Lung macrophages are among the major cells producing TGF-alpha in a lung tissue. A pivotal event in the cascade of pathologic events leading to pulmonary silicosis is the interaction between inhaled silica and macrophages. TGF-alpha may be critical in directing the proliferation of type II pneumocytes that characterize silicosis. An inhalation model of brief exposure of pathogen-restricted male rats to 25 mg/M3 cristobalite, a highly reactive form of silicon dioxide was used to study experimental silicosis. This model is characterized by a rapid, intense, and sustained increase in macrophages, neutrophils, and lymphocytes in both alveolar and interstitial compartments of the lung. TGF-alpha was measured in an A431 cell proliferation assay made specific with the use of anti-TGF-alpha neutralizing antiserum in epithelial lining fluid (ELF) and conditioned media harvested from cultured alveolar and interstitial macrophages. Soluble TGF-alpha levels found in ELF were slightly elevated above control values during the exposure period, then increased 5-fold during the 20 weeks after the 8-day exposure period. Secretion of TGF-alpha by macrophages was elevated during exposure to cristobalite but then fell during the early post exposure period. Marked elevations in TGF-alpha secretion from both interstitial and alveolar macrophages (10- and 12-fold, respectively) occurred 8-16 weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Absher
M
M
Department of Medicine, University of Vermont, Burlington 05405.
Sjöstrand
M
M
Baldor
L C
LC
Hemenway
D R
DR
Kelley
J
J
D000208:Acute Disease; D000818:Animals; D001681:Biological Assay; D008214:Lymphocytes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000378:metabolism*
D016211:Transforming Growth Factor alpha; D012822:Silicon Dioxide