| Title | Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma. | | Author(s) | Schain F, Tryselius Y, Sjöberg J, Porwit A, Backman L, Malec M, Xu D, Vockerodt M, Baumforth KR, Wei W, Murray PG, Björkholm M, Claesson HE | | Institution | Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. | | Source | Int J Cancer 2008 Aug 14. | | 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. LTD(4) stimulated protein release of tumor necrosis factor-alpha, interleukin-6 and -8 by L1236 cells and interleukin-8 by KMH2 cells. Importantly, all these LTD(4)-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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18704935 |
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