114 Scopus citations

Abstract

Human epidermal cells exhibited none of the cytosolic lipoxygenase activity that is prominent in mucosal epithelial cells, but instead contained a microsomal activity that converted arachidonic acid to 12- hydroxyeicosatetraenoic acid (12-HETE). Identification of the extractable 12- HETE-forming activity as a 12-lipoxygenase (distinct from cytochrome P-450) included (S)-12-stereospecificity of product formation, trapping of 12- hydroperoxyeicosatetraneoic acid as an intermediate reaction product, and lack of NADPH dependence for activity. Epidermal cell poly(A)+ RNA contained high levels of a 2.3-kb mRNA that selectively hybridized with human platelet 12-lipoxygenase cDNA, and partial cDNA sequence of this mRNA indicated identity to platelet 12-lipoxygenase. The epidermal 12-lipoxygenase was not recognized by antibodies against the leukocyte-type 12- and 15-lipoxygenases (found in leukocytes, reticulocytes, and mucosal epithelial cells) but was detected by an antiplatelet 12-lipoxygenase antibody. The epidermal 12- lipoxygenase antigen was selectively expressed in germinal layer keratinocytes in healthy and psoriatic skin, and these layers exhibited hyperplasia and increased immunostaining in inflamed psoriatic skin. Together with previous results, these observations indicate that 1) epidermis generates 12-HETE by either cytochrome P-450- or lipoxygenase-based mechanisms depending on reaction conditions, and 2) 12-lipoxygenases (originally described in hematopoietic cell types) may be expressed in at least two distinct isoforms in epithelial barriers in humans, and in the case of the skin, a microsomal (platelet-type) 12-lipoxygenase is selectively overexpressed in germinal layer keratinocytes during psoriatic inflammation.

Original languageEnglish
Pages (from-to)C243-C253
JournalAmerican Journal of Physiology - Cell Physiology
Volume266
Issue number1 35-1
DOIs
StatePublished - 1994

Keywords

  • 12-hydroxyeicosatetraenoic acid
  • arachidonic acid
  • inflammation

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