2 SEPARATE DOMAINS OF LAMININ PROMOTE LUNG ORGANOGENESIS BY DIFFERENT MECHANISMS OF ACTION

被引：46

作者：

SCHUGER, L

SKUBITZ, APN

MORENAS, ADL

GILBRIDE, K

机构：

[1] BOSTON UNIV, SCH MED, DEPT PATHOL & LAB MED, BOSTON, MA 02118 USA

[2] UNIV MINNESOTA, SCH MED, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA

来源：

DEVELOPMENTAL BIOLOGY | 1995年 / 169卷 / 02期

关键词：

D O I：

10.1006/dbio.1995.1166

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Laminin is a major component of basement membranes. We previously reported that the globular region of laminin B chain(s) and the cross region of the A chain play an active role in mouse lung branching morphogenesis. In this study, basic morphogenic cell behaviors modulated by laminin were analyzed in order to elucidate how this glycoprotein promotes lung development. Cocultures of epithelial and mesenchymal cells from mouse fetal lungs were used to determine the effect of site-specific monoclonal antibodies to laminin (AL-1, AL-2, AL-3, AL-4, and AL-5) on epithelial and mesenchymal cell adhesion, proliferation, and organotypic rearrangement. We found that monoclonal antibody AL-1, directed against the cross region of the laminin A chain, inhibited epithelial and mesenchymal cell attachment and had a selective antiproliferative effect on epithelial cells. In contrast, monoclonal antibody AL-5, directed against the globular region of the B chain(s), blocked epithelial cell polarity. Immunohistochemical studies on epithelial-mesenchymal cocultures exposed to monoclonal antibody AL-5 revealed the absence of laminin deposition at the epithelial-mesenchymal interface, whereas type collagen IV was present at this site. These findings suggest that each of the two laminin domains involved in lung development promotes morphogenesis by a different mechanism of action. The cross-region of the A chain mediates cell adhesion and epithelial cell proliferation, whereas the globular region of the laminin B chain(s) is critical for the process of basement membrane assembly and cell polarization. The combined effect of both laminin domains on epithelial and mesenchymal cells and on the interaction between them seems to be essential for normal lung branching morphogenesis. (C) 1995 Academic Press, Inc.

引用

页码：520 / 532

页数：13

共 32 条

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