Effect of recombinant human IL-4 on tryptase, chymase, and Fc epsilon receptor type I expression in recombinant human stem cell factor-dependent fetal liver-derived human mast cells.
The effect of recombinant human IL-4 (rhIL-4) on the development of recombinant human stem cell factor-dependent fetal liver-derived mast cells was examined. RhIL-4 attenuates the number of mast cells that develop, preferentially affecting the MC(T) type of mast cell. Cellular levels of tryptase and chymase mRNA normalized to that of glyceraldehyde-3-phosphate dehydrogenase were not appreciably affected. Tryptase mRNA levels peaked at least 2 wk before tryptase protein and before chymase mRNA and protein, indicating that tryptase mRNA expression is an early marker of commitment to a mast cell lineage. In contrast, alpha-tryptase and beta-tryptase mRNA levels increased and decreased in parallel. The most dramatic effect of rhIL-4 was to induce expression of functional surface Fc epsilonRI. Expression was maximal by 21 days with 20 ng/ml of rhIL-4 and reached a plateau by 2 ng/ml of rhIL-4 at 4 wk. Fc epsilonRI+ cells increased modestly when myeloma IgE was added to the developing mast cells, but increased synergistically when both myeloma IgE and rhIL-4 were present together. Delayed addition of rhIL-4 progressively diminished Fc epsilonRI expression, as did withdrawal of rhIL-4 during the first 2 wk of culture. RhIL-4 selectively increased Fc epsilonRI alpha mRNA levels at least 10-fold. Mast cells developed in the presence of rhIL-4 released tryptase when exposed to anti-Fc epsilonRI alpha. In conclusion, induction of functional Fc epislonRI on recombinant human stem cell factor-dependent human fetal liver-derived mast cells by rhIL-4 harmonizes with the well-accepted ability of this cytokine to enhance IgE production by B cells.
Xia
H Z
HZ
Department of Internal Medicine, Virginia Commonwealth University, Richmond 23298, USA.
Du
Z
Z
Craig
S
S
Klisch
G
G
Noben-Trauth
N
N
Kochan
J P
JP
Huff
T H
TH
Irani
A M
AM
Schwartz
L B
LB
D002478:Cells, Cultured; D053818:Chymases; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000196:embryology; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011961:Receptors, Fc / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D019089:Stem Cell Factor / Q000494:pharmacology*; D053802:Tryptases
D011961:Receptors, Fc; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D015847:Interleukin-4; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases