Interleukin-4 is an autocrine growth factor secreted by the L-428 Reed-Sternberg cell.
Recent evidence indicates that Reed-Sternberg (RS) cells from many cases of Hodgkin's disease have features of activated lymphocytes and that lymphokines from activated lymphocytes induce proliferation of L-428 RS cells. It is shown here that a lymphokine similar to a lymphokine secreted by activated lymphocytes is secreted by L-428 cells. This lymphokine has a molecular weight approximately equal to 68,000 daltons, identical to glycosylated recombinant interleukin-4 (rIL-4), and cross-reacts with monoclonal anti-IL-4 in Western immunoblotting. This Hodgkin's cell growth factor (HCGF) is 100% neutralized by polyclonal anti-IL-4 antibodies and competes for the IL-4 receptor. After acid-elution, the L-428 RS cell has been shown to have 3,396 +/- 120 high-affinity receptor sites/cell. HCGF competes with rIL-4 for this receptor and L-428 cells contain mRNA for IL-4. Although all evidence indicates that IL-4 is an important secreted autocrine growth factor for L-428 RS cells, anti-IL-4 has no effect on the sustained serum-free growth of these Hodgkin's cells, suggesting that either the IL-4 receptor and the IL-4 receptor-growth factor complex are protected from antibody inhibition or other mechanisms are responsible for the sustained proliferation of L-428 RS cells.
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Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
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D000906:Antibodies; D001667:Binding, Competitive; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4