Limits...
Laminin alpha1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.

Schuger L, Skubitz AP, Zhang J, Sorokin L, He L - J. Cell Biol. (1997)

Bottom Line: In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin alpha1, alpha2, and beta/gamma chains.Lung explants exposed to monoclonal antibodies to laminin alpha1 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 alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

ABSTRACT
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 beta1 and gamma1 chains and differ from each other on their alpha chain, which is alpha1 and alpha2 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 alpha1 chain. Synthesis of laminin alpha1 chain however returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical, since laminin alpha1 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 alpha1 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 alpha1, alpha2, and beta/gamma chains. Lung explants exposed to monoclonal antibodies to laminin alpha1 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 alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.

Show MeSH
Histogram showing the percentage of polarized (elongated) and unpolarized (round) peribronchial cells in day 12 embryonic lung explants exposed for 3 d to various anti-LM antibodies and control immunoglobulin. The number of polarized  (elongated) and unpolarized (round) peribronchial mesenchymal  cells was determined on histological sections of the explants.  These were cut longitudinally to and including the full main bronchus. Only the cells closest to the BM of the main bronchus and  its first order branches were quantitated. The bars represent SD.  The means and SD are based on five examples of each treatment.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2139794&req=5

Figure 10: Histogram showing the percentage of polarized (elongated) and unpolarized (round) peribronchial cells in day 12 embryonic lung explants exposed for 3 d to various anti-LM antibodies and control immunoglobulin. The number of polarized (elongated) and unpolarized (round) peribronchial mesenchymal cells was determined on histological sections of the explants. These were cut longitudinally to and including the full main bronchus. Only the cells closest to the BM of the main bronchus and its first order branches were quantitated. The bars represent SD. The means and SD are based on five examples of each treatment.

Mentions: By using this semi-quantitative method, we found a statistically significant difference in the number of elongated versus round peribronchial cells in the explants exposed to 50 or 100 μg/ml of anti-LM α1 chain antibody compared to the other mAbs (Fig. 10). Notice the high percentage of unpolarized peribronchial mesenchymal cells in the lung explants exposed to anti-LM α1 chain antibody (P < 0.005, with Student's t test) and how this is corrected with preincubation of the antibody with LM-1. No significant differences were found in the total number of mesenchymal cells among the explants, including those treated with anti-LM α1 chain (350 ± 45).


Laminin alpha1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.

Schuger L, Skubitz AP, Zhang J, Sorokin L, He L - J. Cell Biol. (1997)

Histogram showing the percentage of polarized (elongated) and unpolarized (round) peribronchial cells in day 12 embryonic lung explants exposed for 3 d to various anti-LM antibodies and control immunoglobulin. The number of polarized  (elongated) and unpolarized (round) peribronchial mesenchymal  cells was determined on histological sections of the explants.  These were cut longitudinally to and including the full main bronchus. Only the cells closest to the BM of the main bronchus and  its first order branches were quantitated. The bars represent SD.  The means and SD are based on five examples of each treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139794&req=5

Figure 10: Histogram showing the percentage of polarized (elongated) and unpolarized (round) peribronchial cells in day 12 embryonic lung explants exposed for 3 d to various anti-LM antibodies and control immunoglobulin. The number of polarized (elongated) and unpolarized (round) peribronchial mesenchymal cells was determined on histological sections of the explants. These were cut longitudinally to and including the full main bronchus. Only the cells closest to the BM of the main bronchus and its first order branches were quantitated. The bars represent SD. The means and SD are based on five examples of each treatment.
Mentions: By using this semi-quantitative method, we found a statistically significant difference in the number of elongated versus round peribronchial cells in the explants exposed to 50 or 100 μg/ml of anti-LM α1 chain antibody compared to the other mAbs (Fig. 10). Notice the high percentage of unpolarized peribronchial mesenchymal cells in the lung explants exposed to anti-LM α1 chain antibody (P < 0.005, with Student's t test) and how this is corrected with preincubation of the antibody with LM-1. No significant differences were found in the total number of mesenchymal cells among the explants, including those treated with anti-LM α1 chain (350 ± 45).

Bottom Line: In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin alpha1, alpha2, and beta/gamma chains.Lung explants exposed to monoclonal antibodies to laminin alpha1 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 alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

ABSTRACT
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 beta1 and gamma1 chains and differ from each other on their alpha chain, which is alpha1 and alpha2 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 alpha1 chain. Synthesis of laminin alpha1 chain however returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical, since laminin alpha1 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 alpha1 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 alpha1, alpha2, and beta/gamma chains. Lung explants exposed to monoclonal antibodies to laminin alpha1 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 alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.

Show MeSH