Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.
Bleomycin causes focally diffuse interstitial fibrosis characterized by increases in the number and volume of contractile filament-laden parenchymal cells, as well as increased parenchymal contractility. However, the origin of these cells and their relationship to altered contractility, remain unknown. We now have used immunohistochemical methods to ask if cells containing smooth muscle actin and myosin are present in involved regions of parenchyma. Staining of the parenchyma of control lungs with a monoclonal antibody against alpha-smooth muscle actin is sparse, consisting of reactivity with the alveolar entrance ring (septal tip) cells as well as occasional reactivity of alveolar wall cells that may represent pericytes or contractile interstitial cells. Increased alpha-smooth muscle actin staining was observed in areas of parenchymal damage in lungs from animals sacrificed between 1 and 4 weeks postbleomycin instillation. This reactivity included altered staining of the airway and vessel smooth muscle coat as well as thickened septal tips. In addition, newly reactive cells were observed in interstitial and intraalveolar regions and in bands of thickened submesothelial tissue. Staining was most intense in the focal fibrotic lesions which are characteristic of this injury. By contrast, parenchymal reactivity with a polyclonal antibody against smooth muscle myosin at the later time points shows only a mild increase in punctate staining in the damaged foci. We hypothesize that the substantial increase in alpha-smooth muscle actin containing cells in fibrotic regions of involved parenchyma after bleomycin injury is responsible for the altered morphologic, biochemical, and mechanical properties that we have observed.
Mitchell
J
J
Department of Physiology & Biophysics, College of Medicine, University of Vermont, Burlington.
Woodcock-Mitchell
J
J
Reynolds
S
S
Low
R
R
Leslie
K
K
Adler
K
K
Gabbiani
G
G
Skalli
O
O
D000199:Actins / Q000032:analysis*; D000818:Animals; D001761:Bleomycin; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008168:Lung / Q000032:analysis* / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000032:analysis*; D009218:Myosins / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms
D000199:Actins; D001761:Bleomycin; D009218:Myosins