HTI56, an integral membrane protein specific to human alveolar type I cells

The alveolar epithelium is composed of two morphologically distinct types of cells, Type I and Type II cells. The thin cytoplasmic extensions of Type I cells cover more than 95% of the internal surface area of the lungs. Type I cells provide the very short diffusion pathway essential for gas exchange. Because there were no biochemical markers specific for human Type I cells, we developed a strategy to produce a monoclonal antibody (MAb) specific for human Type I cells. Isolated human lung cells were used as immunogens; >5000 clones from seven fusions were screened to identify an MAb specific for a 56-kD protein of Type I cells, HTI56. By Western blotting, HTI56 is unique to the lung. By immunoelectron microscopy, it is localized to the Type I cell apical plasma membrane. The pI of HTI56 is 2.5-3.5. HTI56 is glycosylated and has the biochemical characteristics of an integral membrane protein. HTI56 is detectable by Week 20 of gestation and its expression increases in fetal lung explant culture. HTI56 should be useful as a marker for human Type I cells both morphologically and biochemically. It may also be useful in studies of disease and as a marker for lung injury.