Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells.
Although interleukin-4 (IL-4) in mice is known to augment the proliferation of mast cells and to modulate the expression of certain mast cell protease transcripts, its effect on human mast cells is less well understood. The current study examined the effects of recombinant human IL-4 (rhuIL-4) on stem cell factor (SCF)-dependent fetal liver-derived human mast cells in liquid culture. In no case did rhuIL-4 augment proliferation of mast cells. rhuIL-4 selectively inhibited certain aspects of the development of mast cells in cultures of fetal liver cells with rhuSCF. These include lower numbers and percentages of cells expressing tryptase and surface Kit, smaller cells, and lower contents of cells for tryptase, histamine, and Kit. Development of metachromasia was not attenuated. The downregulation of Kit, the surface receptor for SCF, is probably a critical factor, because cells lacking this molecule would not be able to respond to SCF. In contrast to mast cell progenitors, mast cells already developed in vitro from fetal liver cells are relatively resistant to rhuIL-4, but are still dependent for survival on the presence of rhuSCF.
Nilsson
G
G
Department of Medicine, Virginia Commonwealth University, Richmond.
Miettinen
U
U
Ishizaka
T
T
Ashman
L K
LK
Irani
A M
AM
Schwartz
L B
LB
D000032:Abortion, Therapeutic; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002478:Cells, Cultured; D053818:Chymases; D004347:Drug Interactions; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000196:embryology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D019089:Stem Cell Factor; D013997:Time Factors; D053802:Tryptases
D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D015847:Interleukin-4; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases