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Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin lymphoma (cHL) is a malignant disorder with striking inflammatory features. Since cysteinyl leukotrienes (cysLTs) are potent inflammatory mediators it was of interest to study their potential role in the pathogenesis of cHL. We have shown that certain HL cell lines express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. Stimulation of these cells with LTD4 induced a CysLT1 receptor-dependent release of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha. The malignant Hodgkin Reed-Sternberg (H-RS) cells in the majority of the primary cHL biopsies under study also expressed the CysLT1 receptor. Since these cells are surrounded by cysLT-producing eosinophils, macrophages and mast cells, our results suggest that the cysLTs might be of importance for the pathogenesis of cHL (paper I). The cHL cell line L1236 has high expression of 15-lipoxygenase-1 (15-LO-1) and these cells were able to convert arachidonic acid to eoxin (EX) C4, EXD4 and EXE4, pro-inflammatory metabolites recently discovered in human eosinophils and mast cells. Immunohistochemical studies of cHL tumor tissue demonstrated that 15-LO-1 was expressed in primary H-RS cells in the majority of the investigated biopsies. Thus, the expression of 15-LO-1 and the formation of eoxins by H-RS cells are likely to contribute to the inflammatory features of cHL. These findings may have important diagnostic and therapeutic implications (paper II). The expression of the CysLT1 receptor and 15-LO-1 was also elucidated in non-Hodgkin lymphomas (NHLs). The majority of the primary mediastinal B cell lymphomas under study, in contrast to other NHLs, expressed the CysLT1 receptor. Furthermore, T cell-derived anaplastic large cell lymphoma was the only NHL entity shown to express 15-LO-1. Thus, the CysLT1 receptor and 15-LO-1 are potential targets in lymphoma diagnostics and sub-classification (paper III). Finally, we have studied the post-tr

Classical Hodgkin Lymphoma (cHL) is histologically characterized by a minority of malignant cells, the so-called Hodgkin-Reed Sternberg (H-RS) cells, surrounded by inflammatory cells such as T lymphocytes, eosinophils, macrophages and mast cells. It is generally believed that various molecules released by the H-RS cells are of major importance in the pathophysiology of cHL. In paper I, we report a link between inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to tumor cell growth and function in this disease entity. Two HL cell lines, L 1236 and KMH2, were shown to express functional CysLT, receptors, responding with a robust calcium signal upon challenge with LTD4. Incubation of L1236 cells with LTD4 not only stimulated DNA synthesis but also the transcription and protein release of tumor necrosis factor-á, interleukin-6 and -8. Importantly, all these LTD4-induced effects were blocked by the CysLT1, receptor-specific antagonist zafirlukast. Immunohistochemical studies of classical HL biopsies and microarray analysis of laser captured cells revealed that the CysLT1, receptor is expressed also by the Hodgkin Reed-Stemberg cells ex vivo. Since these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as novel mediators in the pathogenesis of classical HL by contributing to the growth and the cytokine features of this tumor. Lipoxygenases are highly regulated enzymes that catalyze the introduction of molecular oxygen in polyunsaturated fatty acids. The lipoxygenases are classified with respect to their positional selectivity of the substrate arachidonic acid. 15-lipoxygenase- 1 (15-LO-1), an enzyme implicated in several pathophysiological conditions, possesses the ability to oxygenate free fatty acids and fatty acids bound to membrane phospholipids. The regulation of the enzymatic activity of membrane associated 15- LO-1 is poorly understood. In paper II we demonstrate

Classical Hodgkin Lymphoma (cHL) is histologically characterized by a minority of malignant cells, the so-called Hodgkin-Reed Sternberg (H-RS) cells, surrounded by inflammatory cells such as T lymphocytes, eosinophils, macrophages and mast cells. It is generally believed that various molecules released by the H-RS cells are of major importance in the pathophysiology of cHL. In paper I, we report a link between inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to tumor cell growth and function in this disease entity. Two HL cell lines, L 1236 and KMH2, were shown to express functional CysLT, receptors, responding with a robust calcium signal upon challenge with LTD4. Incubation of L1236 cells with LTD4 not only stimulated DNA synthesis but also the transcription and protein release of tumor necrosis factor-á, interleukin-6 and -8. Importantly, all these LTD4-induced effects were blocked by the CysLT1, receptor-specific antagonist zafirlukast. Immunohistochemical studies of classical HL biopsies and microarray analysis of laser captured cells revealed that the CysLT1, receptor is expressed also by the Hodgkin Reed-Stemberg cells ex vivo. Since these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as novel mediators in the pathogenesis of classical HL by contributing to the growth and the cytokine features of this tumor. Lipoxygenases are highly regulated enzymes that catalyze the introduction of molecular oxygen in polyunsaturated fatty acids. The lipoxygenases are classified with respect to their positional selectivity of the substrate arachidonic acid. 15-lipoxygenase- 1 (15-LO-1), an enzyme implicated in several pathophysiological conditions, possesses the ability to oxygenate free fatty acids and fatty acids bound to membrane phospholipids. The regulation of the enzymatic activity of membrane associated 15- LO-1 is poorly understood. In paper II we demonstrate

Classical Hodgkin Lymphoma (cHL) is histologically characterized by a minority of malignant cells, the so-called Hodgkin-Reed Sternberg (H-RS) cells, surrounded by inflammatory cells such as T lymphocytes, eosinophils, macrophages and mast cells. It is generally believed that various molecules released by the H-RS cells are of major importance in the pathophysiology of cHL. In paper I, we report a link between inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to tumor cell growth and function in this disease entity. Two HL cell lines, L 1236 and KMH2, were shown to express functional CysLT, receptors, responding with a robust calcium signal upon challenge with LTD4. Incubation of L1236 cells with LTD4 not only stimulated DNA synthesis but also the transcription and protein release of tumor necrosis factor-á, interleukin-6 and -8. Importantly, all these LTD4-induced effects were blocked by the CysLT1, receptor-specific antagonist zafirlukast. Immunohistochemical studies of classical HL biopsies and microarray analysis of laser captured cells revealed that the CysLT1, receptor is expressed also by the Hodgkin Reed-Stemberg cells ex vivo. Since these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as novel mediators in the pathogenesis of classical HL by contributing to the growth and the cytokine features of this tumor. Lipoxygenases are highly regulated enzymes that catalyze the introduction of molecular oxygen in polyunsaturated fatty acids. The lipoxygenases are classified with respect to their positional selectivity of the substrate arachidonic acid. 15-lipoxygenase- 1 (15-LO-1), an enzyme implicated in several pathophysiological conditions, possesses the ability to oxygenate free fatty acids and fatty acids bound to membrane phospholipids. The regulation of the enzymatic activity of membrane associated 15- LO-1 is poorly understood. In paper II we demonstrate