Laminin α1 Chain Synthesis in the Mouse Developing Lung: Requirement for Epithelial–Mesenchymal Contact and Possible Role in Bronchial Smooth muscle Development

The present study shows that whereas a1 and a2 laminins are synthesized in the mouse developing lung and in epithelial-mesenchymal co-cultures derived from it, epithelial and mesenchymal monocultures lose their ability to synthesize the laminin α1 chain. Synthesis of laminin α1 chain, however, returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical since laminin α1 chain is not detected in monocultures exposed to coculture-conditioned medium or in epithelial-mesenchymal cocultures in which heterotypic cell-cell contact is prevented by an interposing filter. Immunohistochemical studies on cocultures treated with brefeldin A, an inhibitor of protein secretion, indicated both epithelial and mesenchymal cells synthesize laminin α1 chain upon heterotypic cell-cell contact. Lung explants exposed to monoclonal antibodies to laminin α1 chain exhibited alterations in peribronchial cell shape and decreased smooth muscle development, as indicated by low levels of smooth muscle a actin and desmin. Taken together, the data suggest that laminin α1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.