Actin content of normal and of bleomycin-fibrotic rat lung.
A large proportion of parenchymal lung is composed of cells with an abundance of actin-containing cytoplasmic microfilaments. This may explain the substantial contractile capability of the tissue, which it appears cannot be ascribed totally to vascular or airway smooth muscle. Parenchymal contractility is increased in bleomycin-induced fibrosis, together with an increase in microfilaments and actin- and myosin-directed immunofluorescence. The present biochemical studies indicate that at least 10% of detergent-extractable protein from peripheral lung is actin. Approximately 71% of this actin is polymerized and 29% is monomeric, on the basis of differential ultracentrifugation. Isoelectric focusing and tryptic peptide analysis show that nonmuscle actin types predominate in the parenchyma, of which approximately 78% is beta-nonmuscle actin and 19% is gamma-nonmuscle actin, together with approximately 3% gamma-smooth muscle actin. Total actin as a percentage of extractable protein was not increased significantly in lungs of rats 4 or 8 wk after bleomycin instillation. Thus, actin per total lung is increased only in proportion to increased total lung weight. There is, in addition, no detectable shift in the beta/gamma actin ratio in the fibrotic lung or increase in percentage of smooth muscle actin. There is, however, a significant 16% decrease in monomeric G-actin and a commensurate significant increase in the percentage of polymerized or F-actin. Therefore, increased contractility and actin-specific immunofluorescence characteristic of fibrotic lung does not appear to be due to increases in total actin but rather to increases in its degree of polymerization, as is found in a variety of remodeling tissues. The consequence of these changes in contractile protein organization to lung function requires further investigation.
D000199:Actins / Q000032:analysis*; D000818:Animals; D001761:Bleomycin; D004591:Electrophoresis, Polyacrylamide Gel; D007525:Isoelectric Focusing; D008168:Lung / Q000032:analysis*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D000199:Actins; D001761:Bleomycin