MYOSIN ISOFORM EXPRESSION IN DEVELOPING AND REMODELING RAT LUNG

The tissue distribution of myosin isoforms was examined in developing smooth muscle of rat lung. Antisera employed included a general smooth muscle myosin antibody (aSMMG) and two smooth muscle myosin isoform s pecific antisera (aSM1 and aSM2). In the pseudoglandular, canalicular, and saccular lung, the isoform-specific aSM1 antiserum was very light ly reactive only with large airway and not reactive with vascular smoo th muscle, whereas aSM2 was unreactive with any lung cells. During the se same stages, the aSMMG serum reacted well with the mesenchymal coat around the larger airways, declining in intensity as the tube size di minished. Vascular smooth muscle elements had only moderate reactivity at this time. In the adult, aSM1 marked airway smooth muscle as well as the tips of the alveolar septae. Vascular reactivity was seen in bo th arterial and venous elements. An identical distribution of reactivi ty was seen for aSMMG. aSM2 reactivity appeared confined primarily to airway smooth muscle and was absent from all but the largest vascular structures. Companion Western blot analyses confirmed the presence of SM1 in fetal and mature tissues as well as the relative lack of SM2 in all but the fully differentiated airways. Lung injury due to intratra cheal instillation of bleomycin is characterized by a proliferation of mesenchymal cells similar to immature smooth muscle cells. These cell s express smooth muscle forms of actin but lacked the mature smooth mu scle myosin isoforms. In summary, differentiation of smooth muscle in the lung proceeds with progressive replacement of nonmuscle isoforms o f myosin with differentiation-specific forms. In this regard, the matu ration of vascular muscle tissue lags behind that of nonvascular (visc eral) muscle structures. Further, the staining of some structures with aSMMG, but not aSM1 or aSM2, early in development suggests either a d istinct organizational pattern or the presence of as yet uncharacteriz ed smooth muscle-specific myosin isoforms.