Modulation of keratin expression in type II pneumocytes by the extracellular matrix

The expression of specific keratin intermediate filaments during differentiation of rat type II pneumocytes in primary culture on various matrices was investigated. Changes in keratin expression were assessed using a monoclonal antikeratin antibody, 24A3, known to react strongly with alveolar epithelial cells in injured lung. Type II cell differentiation was modulated by culture on extracellular matrices known to either accelerate or retard loss of differentiated morphology and metabolic function. During culture on a plastic or fibronectin-rich surface, loss of cell differentiation correlates with increased staining with 24A3 antikeratin antibody by indirect immunofluorescence and with increased abundance of a family of acidic 46,000-dalton keratin isoforms detected in two-dimensional polyacrylamide gels of type II cell cytoskeletal extracts. Loss of type II cell differentiation is retarded or prevented by culture on substrata of purified laminin or of EHS tumor-derived basement membrane (matrigel). 24A3-linked fluorescence and expression of the 46 kDa keratins are reduced in parallel, although at 7 days in culture on matrigel or laminin, keratin expression increases. The results show that changes in type II cell differentiation effected in primary culture by the extracellular matrix correlates with changes in expression of the 24A3-reactive keratins. Loss of differentiated shape and function favors expression of these cytoskeletal antigens, which may provide quantifiable markers of the type II to type I cell transition that occurs during alveolar remodeling.