Effects of interleukin-3 with or without the c-kit ligand, stem cell factor, on the survival and cytoplasmic granule formation of mouse basophils and mast cells in vitro.
We assessed the ultrastructure and the cell-surface expression of receptors for immunoglobulin E (Fc epsilon R), and c-kit, the receptor for stem cell factor (SCF), in mouse basophils and mast cells present in short-term cultures of mouse bone marrow cells in interleukin-3 (IL-3) with or without SCF. Basophils did not develop increased numbers of cytoplasmic granules and underwent apoptosis in cultures containing IL-3 and SCF, whereas mast cells thrived and developed increased numbers of granules. Basophils were nearly all Fc epsilon R+ c-kit- when sorted after culture in IL-3 and SCF; most mast cells were Fc epsilon R+ c-kit+. However, a second population of Fc epsilon R+ c-kit- mast cells was present after culture in IL-3 and SCF. These c-kit receptor-negative mast cells were less mature than c-kit+ mast cells and contained significantly fewer cytoplasmic granules than the c-kit+ mast cells present in the same cultures (P < 0.001). Thus, mouse basophils express little or no c-kit receptor on their surface, nor can they survive for long periods in SCF-supplemented cultures. By contrast, mouse mast cells seem to express the Fc epsilon R early in their development, even before they express detectable c-kit receptors on their surface. IL-3 promotes cytoplasmic granule formation in immature mast cells, but even more granules are formed when c-kit receptor-positive immature mast cells are cultured in both SCF and IL-3.
Dvorak
A M
AM
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
Seder
R A
RA
Paul
W E
WE
Morgan
E S
ES
Galli
S J
SJ
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001853:Bone Marrow / Q000378:metabolism / Q000648:ultrastructure; D001854:Bone Marrow Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000502:physiology*; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019089:Stem Cell Factor; D013234:Stem Cells / Q000166:cytology
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor