Hodgkin/Reed-Sternberg cells induce fibroblasts to secrete eotaxin, a potent chemoattractant for T cells and eosinophils

Blood. 1999 Sep 15;94(6):2065-71.

Abstract

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.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL11
  • Chemokines, CC*
  • Chemotactic Factors, Eosinophil / genetics
  • Chemotaxis, Leukocyte*
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / pathology
  • Fibroblasts / physiology
  • Gene Expression Regulation
  • HeLa Cells
  • Hodgkin Disease / pathology*
  • Humans
  • In Situ Hybridization
  • Lymph Nodes / pathology
  • RNA, Messenger / genetics
  • Reed-Sternberg Cells / pathology*
  • Reed-Sternberg Cells / physiology
  • Skin / cytology*
  • Th2 Cells / physiology
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokines, CC
  • Chemotactic Factors, Eosinophil
  • Cytokines
  • RNA, Messenger