Immunohistochemical localization of thrombomodulin in the stratified epithelium of the rat is restricted to the keratinizing epidermis

The expression and function of thrombomodulin (TM), an endothelial cofactor protein for thrombin-mediated protein C activation, in the epithelium are not fully characterized. This report describes the distribution and localization of TM in the various types of epithelia in the rat by light and electron microscopic immunocytochemistry. TM showed a limited distribution and was expressed by the keratinizing stratified epithelia of the skin, tongue, and esophagus, but was not present on the non-keratinizing epithelia of the vagina, ureter, trachea, stomach, or gut. An identical pattern of TM expression was seen in mucocutaneous junctions, transitional zones from a non-keratinizing stratified epithelium to a keratinizing epithelium at the edge of the eyelid and in the anal canal. As the keratinization of the stratified epithelia proceeded, the staining intensity increased in the transitional zones. Within the keratinizing stratified epithelia, TM staining was limited to the keratinocytes of the spinous layer, the spinous cells. The subcellular localization of TM on the spinous cells was restricted to the plasma membrane facing the intercellular spaces. TM was not detectable on the desmosomes or the two membranes making up the junction, presumably the nexus. The functional significance of TM in keratinizing epithelia is discussed.