Induction of ICAM-1 expression on alveolar epithelial cells during lung development in rats and humans

Intercellular adhesion molecule-1 (ICAM-1) is an adhesion protein involved in immune and inflammatory cell recruitment and activation. In normal, unin flamed adult rat lung, ICAM-1 is expressed at high levels on type I alveola r epithelial cells and is minimally expressed on type II cells. ICAM-1 expr ession by alveolar epithelial cells in vitro is a function of the state of cellular differentiation, and is regulated by factors influencing cell shap e. Based upon this observation, we hypothesized that ICAM-1 expression by f etal lung epithelial cells is developmentally regulated. lo investigate thi s hypothesis, rat and human lung tissues were obtained at time points that represent the canalicular, saccular, and alveolar stages of development. Th e relative expression of ICAM-1 protein and mRNA were determined in rat lun gs from gestational days 18 and 21 (term = 22 days),from day 8 neonatal rat s, and from adult rats. ICBM-I protein was detectable at low level on day 1 8 and increased progressively during development. Relative expression of IC AM-1 protein was maximal in adult lung. Expression of ICAM-1 mRNA parallele d that of ICAM-1 protein. By immunohistochemical methods in rat and human l ung, ICAM-1 was expressed at low level on cuboidal and flattening epithelia l cells in the developing alveolar space at the canalicular and saccular st ages; however, ICAM-1 expression was increased as epithelial cells spread a nd flattened during alveolarization. ICAM-1 was predominantly expressed an type I cells rather than type II cells at the alveolar stage in both the ra t and human lungs. Thus, relative ICAM-1 expression progressively increased during lung development. ICAM-1 expression is correlated with the increase in surface area as alveolar structures develop and type I cell differentia tion takes place. These data indicate that alveolar epithelial cell ICAM-1 expression is developmentally regulated.