Identification of receptors binding fibronectin and laminin on fetal rat lung cells. Caniggia, Isabella, Jason Liu, Robin Han, Jinxia Wang, A. Keith Tanswell, Gordon Laurie & Martin Post. Medical Research Group in Lung Development and the Neonatal Research Division, Department of Paediatrics, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada, Department of Anatomy and Cell Biology, University of Virginia, Charlottesville, Virginia, USA
APStracts 2:0185L, 1995.
Fibronectin and laminin have been implicated in regulating lung morphogenesis. In the present study, the cell surface receptors involved in fetal lung cell binding to laminin and fibronectin were identified. Message for [alpha]5 and [beta]1 integrin subunits were detected in both fetal lung epithelial cells and fibroblasts. The presence of [alpha]5[beta]1 integrin on both cell types was demonstrated by immunocytochemistry and confirmed by cell adhesion experiments with fibronectin and RGD-containing peptides. Epithelial cells adhered more readily to laminin than fibroblasts. The integrin [alpha]4[beta]1, an RGD-independent fibronectin receptor was weakly expressed on either cell type. Both cell types expressed [alpha]6 integrin subunit mRNA and stained immunopositive for the [alpha]6 subunit. Although either cell type expressed non-integrin 67-kd laminin/elastin receptor mRNA, no positive immunoreactivity for this laminin/elastin binding protein was detected. None of these findings explain the enhanced attachment of distal fetal lung epithelial cells to laminin compared with fibroblasts. Previously, we have reported that epithelial cells were enriched in [alpha]3 integrin subunit mRNA and protein expression. Herein, we found that epithelial cell attachment to laminin was nearly completely inhibited by [alpha]3 but only partially by [alpha]6 monoclonal antibodies. A peptide near the globular region at the long arm of the laminin A-chain, which contained the IKVAV sequence, and the laminin A-chain amino acid sequence representing the [alpha]3 1 integrin binding site, inhibited the adherence of epithelial cells to laminin. Fetal lung epithelial cells attached to substrata coated with the [alpha]3 1 integrin binding site peptide and the peptide containing the IKVAV sequence. These data suggest that both fetal lung cell types bind to fibronectin via the fibronectin receptor, [alpha]5 1, and fetal lung epithelial cells interact with laminin via [alpha]3 1 and proteins which recognize the IKVAV containing sequence on the laminin A-chain. 

Received 1 June 1995; accepted in final form 27 September 1995.
APS Manuscript Number L172-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95