DIFFERENTIATION-RELATED EXPRESSION OF ICAM-1 BY RAT ALVEOLAR EPITHELIAL-CELLS

Local regulation of immune and inflammatory responses within the alveo lar space is a critical aspect of normal pulmonary host defense. The t ype I and type II epithelial cells that line the alveolar space are in intimate contact with lymphocytes and macrophages within the alveolar space and are ideally situated to provide regulatory signals to these effector cells. The present studies were undertaken to investigate th e expression by rat alveolar epithelial cells in vitro and in vivo of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule that is involved in migration and activation of T cells and macrophages. An antibody specifically blocking rat ICAM-1 (mAb 1A29) inhibited the ad herence of activated T lymphoblasts to monolayers of type II alveolar epithelial cells. The expression of ICAM-1 protein by alveolar epithel ial cells in vitro was confirmed both by immunofluorescence microscopy and by Western blot analysis. However, in each instance, ICAM-1 was n ot detected in type II cells the day of isolation, but appeared at low levels after 1 day and in abundance throughout the monolayer after 2 days, with sustained expression thereafter. This suggested that ICAM-1 expression might be a type I cell feature, which was induced as isola ted type II cells underwent transformation towards the type I cell-lik e phenotype in vitro. Using immunofluorescence microscopy on frozen se ctions of normal lung, ICAM-1 was found in a linear distribution along the alveolar space, consistent with expression on type I cells. Doubl e staining of lung sections with murine antibody specific for ICAM-1 a nd rabbit antiserum to surfactant apoprotein A, to identify type II ce lls, demonstrated little or no immunostaining for ICAM-1 by type II ce lls. The implication of this work is that alveolar epithelial cells ex press ICAM-1 and thus may provide an important signal regulating the n umber and state of activation of immune effector cells within the alve olar space. Furthermore, high-level expression of ICAM-1 is a differen tiation-related feature of the type I cell phenotype and should be add ed to the list of markers of this poorly characterized cell type.