Hodgkin/Reed-Sternberg cells induce fibroblasts to secrete eotaxin, a potent chemoattractant for T cells and eosinophils.
Hodgkin's disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin's disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin's disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor-alpha (TNF-alpha) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF-alpha by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin's disease by contributing to eosinophil and T-lymphocyte recruitment.
Jundt
F
F
Universitätsklinikum Charité, Robert-Rössle-Klinik, Humboldt University of Berlin, Berlin, Germany. fjundt@mdc-berlin.de
Anagnostopoulos
I
I
Bommert
K
K
Emmerich
F
F
Müller
G
G
Foss
H D
HD
Royer
H D
HD
Stein
H
H
Dörken
B
B
D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000473:pathology* / Q000502:physiology; D012867:Skin / Q000166:cytology*; D018418:Th2 Cells / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D012333:RNA, Messenger