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 specific antisera (aSM1 and aSM2). In the pseudoglandular, canalicular, and saccular lung, the isoform-specific aSM1 antiserum was very lightly reactive only with large airway and not reactive with vascular smooth muscle, whereas aSM2 was unreactive with any lung cells. During these same stages, the aSMMG serum reacted well with the mesenchymal coat around the larger airways, declining in intensity as the tube size diminished. 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 both arterial and venous elements. An identical distribution of reactivity 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 intratracheal instillation of bleomycin is characterized by a proliferation of mesenchymal cells similar to immature smooth muscle cells. These cells express smooth muscle forms of actin but lacked the mature smooth muscle myosin isoforms. In summary, differentiation of smooth muscle in the lung proceeds with progressive replacement of nonmuscle isoforms of myosin with differentiation-specific forms. In this regard, the maturation of vascular muscle tissue lags behind that of nonvascular (visceral) muscle structures. Further, the staining of some structures with aSMMG, but not aSM1 or aSM2, early in development suggests either a distinct organizational pattern or the presence of as yet uncharacterized smooth muscle-specific myosin isoforms.