Mast cell growth-enhancing activity (MEA) stimulates interleukin 6 production in a mouse bone marrow-derived mast cell line and a malignant subline.
A novel mast cell growth-enhancing activity (MEA/P40/interleukin 9 [IL-9]) purified from the conditioned medium of a murine interleukin 2 (IL-2)-dependent Mlsa-specific T-cell line (MLS4.2) was tested for its capacity to induce interleukin 6 (IL-6) production in a mouse bone marrow-derived factor-dependent mast cell line (L138.8A). This interleukin 3 (IL-3)/interleukin 4 (IL-4)/MEA-responsive cell line was demonstrated recently to express IL-6 mRNA and to secrete IL-6 when cultured with IL-3/IL-4. Now we were able to show that conditioned medium from L138.8A mast cells stimulated with MEA alone contained growth factor activity for the IL-6-dependent mouse hybridoma cell line 7TD1 that was completely blocked by the monoclonal anti-IL-6 antibody 6B4. A dose-response study including IL-3, IL-4, and MEA tested either alone or in different combinations revealed that among these growth factors MEA was the most potent inducer of IL-6 in L138.8A cells. Moreover, IL-4 but not IL-3 had a strong synergistic effect on MEA-induced IL-6 production. The autonomous malignant mast cell subline L138Cauto also showed enhanced IL-6 production when stimulated with MEA. Our findings indicate that MEA (IL-9) not only provides a proliferation signal, but also leads to a marked functional activation of responsive mast cells.
Hültner
L
L
GSF-Institute of Experimental Hematology, Munich, Federal Republic of Germany.
Moeller
J
J
D000818:Animals; D001854:Bone Marrow Cells; D004357:Drug Synergism; D015870:Gene Expression; D006825:Hybridomas / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016906:Interleukin-9; D007378:Interleukins / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D015850:Interleukin-6; D016906:Interleukin-9; D007378:Interleukins; D012333:RNA, Messenger; D015847:Interleukin-4