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© The Rockefeller University Press, 0021-9525/1997//553 $5.00
The Journal of Cell Biology, Volume 139, Number 2, , 1997 553-562

Article

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{ddagger}, Jun Zhang*, Lydia Sorokin§, and Li He*

* Department of Pathology and Laboratory Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201; {ddagger} 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}, β, and {gamma} polypeptide chains linked together by disulfide bonds. Laminins-1 and -2 are both composed of β1 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 β/{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.

Abbreviations used in this paper: BM, basement membrane; LM, laminin.

Address all correspondence to Lucia Schuger, Wayne State University School of Medicine, Department of Pathology, Gordon H. Scott Hall of Basic Medical Sciences, 540 East Canfield Street, Detroit, MI 48201. Tel.: (313) 577-5651. Fax: (313) 577-0057.


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