REGULATION OF ALVEOLAR EPITHELIAL-CELL ICAM-1 EXPRESSION BY CELL-SHAPE AND CELL-CELL INTERACTIONS

In normal lung, intercellular adhesion molecule 1 (ICAM-1) is expresse d at high levels on thin type I alveolar epithelial cells, but is mini mally expressed on cuboidal type II cells. ICAM-1 is induced in primar y culture on tissue culture-treated plastic as type II cells undergo t ransition toward a type I cell-like phenotype. We hypothesized that al veolar epithelial cell expression of ICAM-1 might be regulated in part by signals that influence the state of differentiation of these cells . We found that rat type II cells that were cultured as aggregates of cuboidal cells on a hydrated basement membrane gel (Matrigel) or on fl oating type I collagen gels, expressed markedly less ICAM-1 protein an d mRNA compared with cells that had spread on plastic. In contrast, ty pe II cells that had spread as monolayers on dishes coated with baseme nt membrane proteins in planar configuration demonstrated ICAM-1 expre ssion comparable to that of cells on plastic alone. Thus regulation of alveolar epithelial cell expression of this immunologically important adhesion molecule involves complex spatial interactions of the cells with the basement membrane and other epithelial cells.