Generation of a novel stem cell factor-dependent mast cell progenitor.
Tissue mast cell development requires stem cell factor (SCF), whereas helminth-induced intestinal mucosal mast cell hyperplasia also requires T cell-derived factors such as IL-3. We generated progenitor mast cells (PrMC) from mouse bone marrow cells (BMC) in vitro with a triad of SCF, IL-6, and IL-10 that exhibit IL-3-mediated mitogenic and maturation responses. SCF/IL-6/IL-10 transiently elicited a cell subpopulation with the phenotype (c-kit(high)Thy-1(low)) of fetal blood promastocytes at 3 wk of culture that progressed within 1 wk to FcepsilonRI-bearing PrMC, designated PrMCTriad. PrMCTriad lacked mouse mast cell carboxypeptidase A (mMC-CPA) protein, required SCF for IL-3-driven thymidine incorporation, and responded to SCF plus IL-3 with strong mMc-CPA immunoreactivity, clarifying distinct sequential roles for SCF and IL-3 in mast cell development. PrMCTriad, arising from BMC through promastocytes, are metamastocytes that acquire microenvironmentally determined phenotypic features.
Yuan
Q
Q
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Gurish
M F
MF
Friend
D S
DS
Austen
K F
KF
Boyce
J A
JA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000502:physiology; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D019089:Stem Cell Factor / Q000502:physiology*; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D013936:Thymidine / Q000378:metabolism
D007377:Interleukin-3; D019089:Stem Cell Factor; D013936:Thymidine