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

The alveolar epithelium is composed of two morphologically distinct types o f 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 exchang e. Because there were no biochemical markers specific for human Type I cell s, 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 crones from seven fusions were screened to identify an MAb specific f or a 56-kD protein of Type I cells, HTI56. By Western blotting, HTI56 is un ique 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 glycos ylated and has the biochemical characteristics of an integral membrane prot ein. HTI56 is detectable by Week 20 of gestation and its expression increas es in fetal lung explant culture. HTI56 should be useful as a marker for hu man Type I cells both morphologically and biochemically. It may also be use ful in studies of disease and as a marker for lung injury.