This proposal has as its goal the development and characterization of new nonsurfactant related markers of pulmonary alveolar type 2 and type 1 cells and the use of these markers to explore the in vitro and in vivo biology of the alveolar epithelium. The cell surface binding of sugar specific lectins and a newly described monoclonal antibody will be evaluated in the intact lung. This information will be transfered to isolated type 2 cells whose differentiated cell profile as defined by lectin binding, surfactant and matrix secretory products and ultrastructure will be characterized. The change of this profile with time in culture will be studied and a similar cell profile of the flat alveolar type 1-like cell will be defined. In vitro modulators of this time related change e.g. cell shape, matrix and media additives will be evaluated in order to develop insights into the factors which influence type 2 cell maturation or transition in vitro. Maturation and transition related lectin binding glycoproteins will be identified, isolated and used to raise monoclonal antibodies to cell specific antigens. These antibodies as well as other markers of cell differentiation will then be applied to several in vivo settings which are characterized by type 2 cell maturation or type 2 cell transition to type 1 cells in order to test the validity of the non-surfactant markers of cell differentiation. These studies should provide new cell specific markers of differentiated alveolar type 2 and type 1 cells which can be used to further explore the biology of these cells and provide insights into ways of influencing their state of differentiation.
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