LEUKOTRIENE A(4) HYDROLASE IN HUMAN SKIN

The biochemical properties and immunohistochemical localization of leu kotriene (LT) A(4) hydrolase were investigated in human skin. The acti vity of LTA(4) hydrolase, which catalyzes the hydrolysis of LTA(4) to LTB(4), the most chemotactic compound known, was detected in the 100,0 00 X g supernatant of homogenates of human epidermis and a transformed epidermal cell line (HSC-1). No significant LTA(4) hydrolase activity was detected in human whole skin or dermis. The enzymatic properties of LTA(4) hydrolase isolated from human keratinocytes and peripheral l eukocytes were similar. Their activities were inhibited by bestatin an d captopril, and they were completely absorbed by anti-human LTA(4) hy drolase antibody. By immunoblotting analysis using this antibody, LTA( 4) hydrolase was detected as a 70-kDa protein in human epidermis and H SC-1 and was found to be similar to the enzyme detected in peripheral mononuclear leukocytes. In human dermis, LTA(4) hydrolase was barely d etected by Western blotting. On the other hand, LTA(4) hydrolase was d emonstrated in the cytoplasm of keratinocytes in the epidermis, and in fibroblasts, infiltrating and endothelial cells in the dermis of norm al human skin by immunohistochemical analysis using the immunoperoxida se method. These results suggest that LTB(4) can be generated from LTA (4) by LTA(4) hydrolase in keratinocytes as well as fibroblasts, infil trating and endothelial cells in the dermis of human skin.