SYNTHESIS AND EXPRESSION OF LAMININ DURING HUMAN FETAL LUNG DEVELOPMENT

Backgrounds: The lung develops by epithelial tubes budding and branchi ng into a flexible mesenchyme. This growth is associated with the remo delling of the epithelial basement membrane, of which laminin is a maj or component. Methods: Both the synthesis and expression of laminin we re studied in the human lung between 10 and 31 weeks of gestation, usi ng in situ hybridization and immunohistochemistry. Results: The synthe sis of the beta chain was active in the epithelial and surrounding mes enchymal cells. The mRNAs coding for the gamma chain were less abundan t and mainly found in the epithelium. The synthesis of these two chain s continued throughout gestation, and no significant difference in the density of hybridization grains could be detected between the tips of the expanding buds and the proximal portions. Immunohistochemical loc alization of laminin showed important modifications of the basement me mbrane during gestation. In the first part of the pseudoglandular stag e the epithelial basement membrane stained continuously for laminin. L ater, the basement membrane was labelled in a graded fashion: at the a pex of the growing buds the staining became weak with focal disruption s. Both epithelial and mesenchymal synthesis of laminin remained activ e, while the polypeptide was undetectable using immunohistochemistry. Conclusions: These findings suggest that the remodelling of the baseme nt membrane during human lung morphogenesis is probably not related to a decreasing synthesis of laminin, but to either a proteolytic degrad ation or the assembly of an inadequate complex undetectable with the p olyclonal antibody antilaminin. (C) 1995 Wiley-Liss, Inc.