The type II pneumocyte as a model of lung cell interaction with the extracellular matrix

The influence of the extracellular matrix on differentiation and function of type II pneumocytes was investigated. Cells cultured on a plastic surface lost differentiated characteristics as they assumed a flattened, more attenuated phenotype. By the third day in primary culture, as the cells became less responsive to beta-adrenergic agonists, synthesis and secretion of phosphatidylcholine decreased and lamellar body content declined. Concomitantly, incorporation of [3H]thymidine into cellular DNA increased more than 10-fold. On a surface rich in fibronectin (FN), these transitions in form and function were accelerated. The effects of FN alone were similar to those of a FN-rich matrix deposited by type II cells cultured on plastic. These effects were inhibited when the FN surface was treated with anti-FN, or when the matrix was digested with proteases. In contrast, a laminin-rich matrix helped to maintain typical type II cell morphology and metabolism during culture. This effect was most evident in pneumocytes plated on matrigel (MG), a laminin-rich basement membrane-like gel formed from an extract of a mouse EHS sarcoma. MG inhibited cell flattening and the associated increase in thymidine incorporation; loss of differentiation on plastic was halted when the cells were overlaid with MG. Soluble components released from MG permitted cell flattening but, similar to complete MG, maintained low thymidine incorporation as time in culture was extended. These results show that both morphology and metabolism of cultured type II pneumocytes are influenced by the extracellular matrix.