leukotriene-a4 and Psoriasis

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 micrograms 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 micrograms LTB4/mg enzyme per min) compared with matched uninvolved psoriatic skin (16.4 +/- 3.5 micrograms LTB4/mg enzyme per min), but was decreased only insignificantly compared with normal skin (12.4 +/- 1.8 micrograms 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 microgram enzyme/mg protein in normal lymphocytes and 1.4 +/- 0.3 microgram 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 micrograms 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.

Topics: Animals; Epoxide Hydrolases; Humans; Immunohistochemistry; Leukotriene A4; Leukotriene B4; Lymphocytes; Osmolar Concentration; Psoriasis; Rabbits; Skin; Staining and Labeling

The recent definition of the pathways of generation and structures of diverse products of the lipoxygenation of arachidonic acid has established the identity of a new family of mediators of hypersensitivity and inflammation. Studies of the effects of these mediators have shown that leukotrienes C, D, and E, the constitutents of the slow-reacting substance of anaphylaxis (SRS-A), are extremely potent smooth muscle contractile and vasoactive factors. Leukotriene B is a highly active stimulus of neutrophil and eosinophil functions and suppresses the immunological capabilities of T lymphocytes. The development of specific and sensitive radioimmunoassays has permitted the detection of elevated concentrations of leukotrienes in tissues or exudates in several diseases, including asthma, diverse allergic states, adult respiratory distress syndrome, psoriasis, spondyloarthritis, and gout. The application of selective inhibitors and antagonists of leukotrienes will clarify their pathogenetic contributions in human diseases and may yield new therapeutic approaches.

Topics: Arachidonate Lipoxygenases; Arachidonic Acids; Arthritis; Asthma; Cystic Fibrosis; Humans; Hypersensitivity; Leukotriene A4; Leukotriene B4; Leukotriene E4; Lipoxygenase; Psoriasis; SRS-A; Tears