Hodgkin Reed-Sternberg cells express 15-lipoxygenase-1 and are putative producers of eoxins in vivo: novel insight into the inflammatory features of classical Hodgkin lymphoma.
Classical Hodgkin lymphoma has unique clinical and pathological features and tumour tissue is characterized by a minority of malignant Hodgkin Reed-Sternberg cells surrounded by inflammatory cells. In the present study, we report that the Hodgkin lymphoma-derived cell line L1236 has high expression of 15-lipoxygenase-1 and that these cells readily convert arachidonic acid to eoxin C(4), eoxin D(4) and eoxin E(4). These mediators were only recently discovered in human eosinophils and mast cells and found to be potent proinflammatory mediators. Western blot and immunocytochemistry analyses of L1236 cells demonstrated that 15-lipoxygenase-1 was present mainly in the cytosol and that the enzyme translocated to the membrane upon calcium challenge. By immunohistochemistry of Hodgkin lymphoma tumour tissue, 15-lipoxygenase-1 was found to be expressed in primary Hodgkin Reed-Sternberg cells in 17 of 20 (85%) investigated biopsies. The enzyme 15-lipoxygenase-1, however, was not expressed in any of 10 biopsies representing nine different subtypes of non-Hodgkin lymphoma. In essence, the expression of 15-lipoxygenase-1 and the putative formation of eoxins by Hodgkin Reed-Sternberg cells in vivo are likely to contribute to the inflammatory features of Hodgkin lymphoma. These findings may have important diagnostic and therapeutic implications in Hodgkin lymphoma. Furthermore, the discovery of the high 15-lipoxygenase-1 activity in L1236 cells demonstrates that this cell line comprises a useful model system to study the chemical and biological roles of 15-lipoxygenase-1.
Claesson
Hans-Erik
HE
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, and Orexo AB, Uppsala, Sweden. hans-erik.claesson@ki.se <hans-erik.claesson@ki.se>
Griffiths
William J
WJ
Brunnström
Asa
A
Schain
Frida
F
Andersson
Erik
E
Feltenmark
Stina
S
Johnson
Hélène A
HA
Porwit
Anna
A
Sjöberg
Jan
J
Björkholm
Magnus
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001093:Arachidonate 15-Lipoxygenase / Q000032:analysis / Q000378:metabolism*; D001706:Biopsy; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D017998:Leukotriene D4 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D017999:Leukotriene E4 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D015289:Leukotrienes / Q000096:biosynthesis* / Q000737:chemistry; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000201:enzymology*
C531124:14-cysteinyl-15-hydroxy-5,8,10,12-eicosatetraenoic acid; C531123:14-cysteinylglycyl-15-hydroxy-5,8,10,12-eicosatetraenoic acid; D015289:Leukotrienes; C526311:eoxin C4; D017998:Leukotriene D4; D017999:Leukotriene E4; D001093:Arachidonate 15-Lipoxygenase