Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma

Research output: Contribution to journalArticle

Authors

  • F Schain
  • Y Tryselius
  • J Sjoberg
  • A Porwit
  • L Backman
  • M Malec
  • D Xu
  • M Bjorkholm
  • HE Claesson

Colleges, School and Institutes

Abstract

Classical Hodgkin lymphoma (cHL) is characterized histologically by a minority of malignant Hodgkin Reed-Sternberg cells surrounded by abundant inflammatory cells, generally believed to be of major importance in the pathophysiology of the disease. Here, we present data that link inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to the pathogenesis of cHL. Two HL cell lines, L1236 and KMH2, were shown to express functional CysLT(1) receptors, responding with a robust calcium signal upon leukotriene (LT) D-4 challenge. LTD4 stimulated protein release of tumor necrosis factor-alpha, interleukin-6 and -8 by L1236 cells and interleukin-8 by KMH2 cells. Importantly, all these LTD4-induced effects were blocked by the CysLT(1) receptor-specific antagonist zafirlukast. Immunohistochemical studies of cHL biopsies and microarray analysis of microdissected cells revealed that the CysLT(1) receptor is expressed also by primary Hodgkin Reed-Sternberg cells. As these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as mediators in the pathogenesis of cHL, contributing to the aberrant cytokine network of this lymphoma. (C) 2008 Wiley-Liss, Inc.

Details

Original languageEnglish
Pages (from-to)2285-2293
Number of pages9
JournalInternational Journal of Cancer
Volume123
Issue number10
Publication statusPublished - 1 Nov 2008

Keywords

  • cytokines, leukotrienes, cysteinyl leukotriene receptors, Hodgkin lymphoma, chemokines