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J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/10/553/10 $2.00
Volume 139, Number 2, October 20, 1997 553-562

Laminin alpha 1 Chain Synthesis in the Mouse Developing Lung: Requirement for Epithelial-Mesenchymal Contact and Possible Role in Bronchial Smooth muscle Development

Lucia Schuger,* Amy P.N. Skubitz,Dagger Jun Zhang,* Lydia Sorokin,§ and Li He*

* Department of Pathology and Laboratory Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201; Dagger  Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455; and § Connective Tissue Department, Institute for Experimental Medicine, Erlangen 91054, Germany

Laminins, the main components of basement membranes, are heterotrimers consisting of alpha , beta , and gamma  polypeptide chains linked together by disulfide bonds. Laminins-1 and -2 are both composed of beta 1 and gamma 1 chains and differ from each other on their alpha  chain, which is alpha 1 and alpha 2 for laminin-1 and -2, respectively. The present study shows that whereas laminins-1 and -2 are synthesized in the mouse developing lung and in epithelial-mesenchymal cocultures derived from it, epithelial and mesenchymal monocultures lose their ability to synthesize the laminin alpha 1 chain. Synthesis of laminin alpha 1 chain however returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical, since laminin alpha 1 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 alpha 1 chain upon heterotypic cell- cell contact. In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin alpha 1, alpha 2, and beta /gamma chains. Lung explants exposed to monoclonal antibodies to laminin alpha 1 chain exhibited alterations in peribronchial cell shape and decreased smooth muscle development, as indicated by low levels of smooth muscle alpha  actin and desmin. Taken together, our studies suggest that laminin alpha 1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.


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