Expression of von Hippel-Lindau protein in normal and pathological human tissues

To examine the localization of von Hippel-Lindau (VHL) protein in human tis sues, we produced four novel monoclonal antibodies against human VHL protei n. Western blot analysis revealed that two of these antibodies recognized t he epitope in amino acid sequence 60-89 of the VHL protein and the others r ecognized sequences 54-60 and 189-213. In a wild-type VHL gene-transfected cell line, immunocytochemistry and immunoelectron microscopy demonstrated t he intracytoplasmic localization of VHL protein, particularly in mitotic ce lls. In normal human tissues, VHL protein was detected immunohistochemicall y in epithelial cells covering the body surface and the alimentary, respira tory, and genitourinary tracts; in secretory epithelial cells of exocrine a nd endocrine organs; in parenchymal cells of visceral organs; in cardiomyoc ytes; in neurons in nervous tissue; in lymphocytes in lymphoid tissue; and in macrophages. In pathological specimens, VHL protein was expressed in VHL -related tumor, as well as in endothelial cells, fibroblasts, and pericytes , all of which are involved in active angiogenesis. These findings suggest that these monoclonal antibodies can be useful for various immunological as says and that the VHL protein plays fundamental roles in physiological and pathological situations, especially in neovascularization.