Induction by IL-9 and suppression by IL-3 and IL-4 of the levels of chromosome 14-derived transcripts that encode late-expressed mouse mast cell proteases.
Immature, rIL-3-dependent mouse bone marrow-derived mast cells (BMMC) contain high steady-state levels of the mouse mast cell protease (mMCP) 5 transcript but undetectable levels of the mMCP-1, mMCP-2, or mMCP-4 transcripts even though all four of their genes reside at a locus on chromosome 14. These mast cells can be induced by recombinant c-kit ligand (rKL) to obtain high steady-state levels of the mMCP-4 transcript and by rIL-10 to obtain high steady-state levels of the mMCP-1 and mMCP-2 transcripts. rIL-3 and rKL both elicit the differentiation of progenitor cells into immature BMMC and then stimulate their proliferation. We now report that although rIL-9 alone has no effect on BMMC proliferation as assessed by their incorporation of [3H]thymidine, rIL-9 in combination with rKL enhances the long term viability of BMMC. Furthermore, rIL-9 in the presence of rKL stimulates mouse BMMC to undergo a phenotypic change by inducing accumulation of high steady-state levels of the mMCP-1 and mMCP-2 transcripts. In contrast, in BMMC, the presence of rIL-4 suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts, the rIL-10-induced accumulation of the mMCP-1 and mMCP-2 transcripts, and the rKL-induced accumulation of the mMCP-4 transcript, but not the rIL-3-induced accumulation of the mMCP-5 transcript. The presence of rIL-3 also suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts. Because of their counter-regulatory actions on the steady-state levels of transcripts that encode three late-expressed serine proteases in BALB/cJ mice, rIL-4 and rIL-3 both inhibit the final stages of differentiation and maturation of mast cells. Because rIL-4, unlike rIL-3, is neither an inducer of early-expressed proteases nor alone a proliferative factor for BMMC, the counterregulatory actions of rIL-3 and rIL-4 on differentiation and maturation of these mouse mast cells are independent of their other functions.
Eklund
K K
KK
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Ghildyal
N
N
Austen
K F
KF
Stevens
R L
RL
D000818:Animals; D002478:Cells, Cultured; D002875:Chromosomes; D053818:Chymases; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006632:Histamine / Q000032:analysis; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics*; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D016906:Interleukin-9; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D015847:Interleukin-4; D006632:Histamine; D012697:Serine Endopeptidases; C083294:chymase 2; C066932:mast cell protease 4; D053818:Chymases; C509229:Cma2 protein, mouse