Leukotriene A4 hydrolase in human skin.
The biochemical properties and immunohistochemical localization of leukotriene (LT) A4 hydrolase were investigated in human skin. The activity of LTA4 hydrolase, which catalyzes the hydrolysis of LTA4 to LTB4, the most chemotactic compound known, was detected in the 100,000 x g supernatant of homogenates of human epidermis and a transformed epidermal cell line (HSC-1). No significant LTA4 hydrolase activity was detected in human whole skin or dermis. The enzymatic properties of LTA4 hydrolase isolated from human keratinocytes and peripheral leukocytes were similar. Their activities were inhibited by bestatin and captopril, and they were completely absorbed by anti-human LTA4 hydrolase antibody. By immunoblotting analysis using this antibody, LTA4 hydrolase was detected as a 70-kDa protein in human epidermis and HSC-1 and was found to be similar to the enzyme detected in peripheral mononuclear leukocytes. In human dermis, LTA4 hydrolase was barely detected by Western blotting. On the other hand, LTA4 hydrolase was demonstrated in the cytoplasm of keratinocytes in the epidermis, and in fibroblasts, infiltrating and endothelial cells in the dermis of normal human skin by immunohistochemical analysis using the immunoperoxidase method. These results suggest that LTB4 can be generated from LTA4 by LTA4 hydrolase in keratinocytes as well as fibroblasts, infiltrating and endothelial cells in the dermis of human skin.
Ikai
K
K
Department of Dermatology, Kyoto University Faculty of Medicine, Japan.
Okano
H
H
Horiguchi
Y
Y
Sakamoto
Y
Y
D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology; D002460:Cell Line; D002461:Cell Line, Transformed; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology / Q000473:pathology; D004851:Epoxide Hydrolases / Q000032:analysis*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000201:enzymology* / Q000473:pathology
D011480:Protease Inhibitors; D004281:Docosahexaenoic Acids; D002216:Captopril; D015118:Eicosapentaenoic Acid; D004851:Epoxide Hydrolases; D007930:Leucine; C012211:ubenimex; C043134:leukotriene A4 hydrolase