LTA4 hydrolase in human skin: decreased activity,but normal concentration in lesional psoriatic skin

Leukotriene A₄ (LTA₄) hydrolase which transforms LTA₄ into the proinflammatory compound LTB₄ has been identified in human epidermis. The purpose of this study was to investigate the potential role of this enzyme in psoriasis, in which LTB₄ is present in biologically active concentrations. The concentration and activity of LTA₄ 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 immunohistochemical staining of skin biopsies. Immunohistochemically LTA₄ hydrolase was localized predominantly in the basal and spinous layers in normal skin and in involved and uninvolved psoriatic skin. The LTA₄ hydrolase content varied between 2.8 and 3.1 μg enzyme/mg protein and was found to be similar in normal and psoriatic skin, involved as well as uninvolved. In contrast, the activity of the enzyme was decreased significantly in involved psoriatic skin (9.9±2.1 μg LTB₄/mg enzyme per min) compared with matched uninvolved psoriatic skin (16.4±3.5 μg LTB₄/mg enzyme per min), but was decreased only insignificantly compared with normal skin (12.4±1.8 μg LTB₄/mg enzyme per min). It was found that the conversion of LTA₄ to LTB₄ results in inactivation of LTA₄ hydrolase activity. This finding is compatible with the idea that the decreased LTA₄ hydrolase activity in involved psoriatic skin reflects transcellular LTB₄ formation in vivo. In peripheral lymphocytes the enzyme content was 1.3±0.3 μg enzyme/mg protein in normal lymphocytes and 1.4±0.3 μg enzyme/mg protein in psoriatic lymphocytes, which was significantly lower than in the skin. In contrast, the specific LTA₄ hydrolase activities in normal and psoriatic lymphocytes (23.4±1.3 and 21.3±1.7 μg LTB₄/mg enzyme per min) were significantly higher than in normal skin. These findings may indicate the existence of LTA₄ hydrolase isoforms in human lymphocytes and human skin.