EPIDERMAL-CELL MIGRATION AND HEALING OF THE TYMPANIC MEMBRANE - AN IMMUNOHISTOCHEMICAL STUDY OF CELL-PROLIFERATION USING BROMODEOXYURIDINE LABELING

A monoclonal antibody against bromodeoxyuridine (BrdU) was used to investigate cell proliferation in the tympanic membrane of white rabbits. The BrdU-labeled cells were observed mainly in the epidermis of the annulus, around the malleus handle, and in the anterior and posterior superior quadrants of the normal rabbit tympanic membrane at 2 hours after BrdU injection. At 5 days the localization of the BrdU-labeled cells had changed centrifugally from the malleus handle toward the annulus. This change in the distribution of BrdU-labeled cells suggested that epidermal cell migration is caused by cell proliferation and insertion of newly proliferated epidermal cells at the proliferation center. Immunohistochemical observation of BrdU-labeled cells in the artificially perforated tympanic membrane suggested that the process of healing of the perforation may be as follows. Epidermal cell proliferation in the whole tympanic membrane is accelerated by the perforation stimulus. Then the proliferated epidermal cells migrate to the edge of the perforation. In contrast, proliferation of connective tissue cells and mucosal cells is stimulated only around the perforation, and cooperates with the proliferated epidermal cells to close the perforation.