LTA(4) HYDROLASE IN HUMAN SKIN - DECREASED ACTIVITY, BUT NORMAL CONCENTRATION IN LESIONAL PSORIATIC SKIN - EVIDENCE FOR DIFFERENT LTA(4) HYDROLASE ACTIVITY IN HUMAN-LYMPHOCYTES AND HUMAN SKIN

Leukotriene A(4) (LTA(4)) hydrolase which transforms LTA(4) into the p roinflammatory compound LTB(4) has been identified in human epidermis. The purpose of this study was to investigate the potential role of th is enzyme in psoriasis, in which LTB(4) is present in biologically act ive concentrations. The concentration and activity of LTA(4) hydrolase was determined in normal skin and in matched samples of involved and uninvolved psoriatic skin. The enzyme content was determined using an affinity-purified antibody. This antibody was also used for immunohist ochemical staining of skin biopsies. Immunohistochemically LTA(4) hydr olase was localized predominantly in the basal and spinous layers in n ormal skin and in involved and uninvolved psoriatic skin. The LTA(4) h ydrolase content varied between 2.8 and 3.1 mu g enzyme/mg protein and was found to be similar in normal and psoriatic skin, involved as wel l as uninvolved. In contrast, the activity of the enzyme was decreased significantly in involved psoriatic skin (9.9 +/- 2.1 mu g LTB(4)/mg enzyme per min) compared with matched uninvolved psoriatic skin (16.4 +/- 3.5 mu g LTB(4)/mg enzyme per min), but was decreased only insigni ficantly compared with normal skin (12.4 +/- 1.8 mu g LTB(4)/mg enzyme per min). It was found that the conversion of LTA(4) to LTB(4) result s in inactivation of LTA(4) hydrolase activity. This finding is compat ible with the idea that the decreased LTA(4) hydrolase activity in inv olved psoriatic skin reflects transcellular LTB(4) formation in vivo. In peripheral lymphocytes the enzyme content was 1.3 +/- 0.3 mu g enzy me/mg protein in normal lymphocytes and 1.4 +/- 0.3 mu g enzyme/mg pro tein in psoriatic lymphocytes, which was significantly lower than in t he skin. In contrast, the specific LTA(4) hydrolase activities in norm al and psoriatic lymphocytes (23.4 +/- 1.3 and 21.3 +/- 1.7 mu g LTB(4 )/mg enzyme per min) were significantly higher than in normal skin. Th ese findings may indicate the existence of LTA(4) hydrolase isoforms i n human lymphocytes and human skin.