Integrin mediation of type ii cell adherence to provisional matrix
proteins.
Kim, Hyun Joo, David H. Ingbar, and Craig A. Henke.
Department of Medicine, University of Minnesota Medical School,
Minneapolis, MN, 55455
APStracts 3:0064L, 1996.
Acute lung injury causes type I alveolar epithelial cell death,
denudation of the alveolar basement membrane, and alveolar flooding
with serum proteins, including fibronectin and fibrinogen.
Fibronectin and polymerized fibrin are two components of the
provisional matrix that coat the denuded alveolus. For successful
restoration of normal architecture, the alveolar epithelium must be
regenerated from progenitor type II alveolar cells. We examined
whether type II alveolar cells adhere to the provisional matrix
proteins fibronectin, fibrinogen, and fibrin, and whether integrins
mediate this adherence. Adhesion assays of rat type II cells to the
provisional matrix proteins were performed along with inhibition
studies. Both freshly isolated and cultured rat type II cells adhered
to fibronectin and fibrinogen in a concentration dependent manner.
This adhesion occurred more avidly than adhesion to the basement
membrane proteins laminin and type IV collagen. Freshly isolated type
II cells also adhered to fibrin gels. Preincubation with synthetic
RGD (arginine-glycine-aspartic acid) peptide specifically blocked
adhesion to fibronectin, fibrinogen and fibrin. Immunofluorescent
flow cytometry (FACS) and Western analysis indicated that rat type II
epithelial cells expressed the [beta]1 integrin subunit and
[alpha]v[beta]3 integrin. Anti- [beta]1 integrin monoclonal antibody
(MoAb) partially blocked type II cell adhesion to fibronectin, while
anti- [alpha]v[beta]3 integrin MoAb partially blocked type II cell
adhesion to fibronectin and fibrinogen. These results indicate that
type II cells adhere to the provisional matrix proteins fibronectin,
fibrinogen, and fibrin, and that it is partially mediated by an
integrin RGD- dependent mechanism. This study provides the first
evidence of: type II cell adhesion to fibrin gels and vitronectin;
[beta]1 integrin and [alpha]v[beta]3 integrin mediation of type II
cell adhesion; and the presence of the [alpha]v[beta]3 integrin on
type II epithelial cells.
Received 28 September 1995; accepted in final form 16 April 1996.
APS Manuscript Number L290-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96