Membrane-bound stem cell factor is the major but not only driver of fibroblast-induced murine skin mast cell differentiation

2017 ◽  
Vol 26 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Mandy Leist ◽  
Cathleen Annett Sünder ◽  
Sebastian Drube ◽  
Carolin Zimmermann ◽  
Astrid Geldmacher ◽  
...  
Blood ◽  
1995 ◽  
Vol 85 (1) ◽  
pp. 57-65 ◽  
Author(s):  
D Rennick ◽  
B Hunte ◽  
G Holland ◽  
L Thompson-Snipes

Stem cell factor (SCF) possesses many mast cell-stimulating activities, including the ability to support the growth of mucosal-like mast cells (MMCs) and connective tissue mast cells (CTMCs). However, this study shows that, in the absence of accessory cells, SCF does not stimulate the clonal growth of primitive mast cell progenitors. Nevertheless, SCF exhibited potent growth-promoting effects when combined with the cytokines interleukin-3 (IL-3), interleukin-4 (IL-4), and interleukin- 10 (IL-10). Our comparative studies have shown that optimal mast cell colony formation occurs when both IL-4 and IL-10 are combined with SCF. However, in the presence of SCF, these two cofactors appear to mediate different effects. IL-4 was more efficient than IL-10 in costimulating the initiation of SCF-dependent colony formation by mast cell progenitors and in sustaining the proliferation of newly generated progeny. On the other hand, IL-4 was less efficient than IL-10 in supporting mast cell differentiation, as evidenced by morphology, cell enlargement, and granule production. Although the actions of IL-4 and IL-10 were not equivalent, additional experiments indicated that their ability to serve as early- and late-acting factors, respectively, were complimentary. We have also found that the mast cells generated in colonies stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6–8 pg per cell). None of the mast cells generated in our cultures synthesized heparin. A phenotypic change from safranin- negative to safranin-positive cells associated with heparin-producing CTMCs was accomplished after coculture of the mast cells with fibroblast cell lines derived from normal mice or from SI/SId mice plus soluble factors. Collectively, our observations demonstrate that SCF acts as a competence factor for mast cell progenitor growth. In addition, the ability of SCF to support certain stages of mast cell differentiation is profoundly influenced by interactions with specific cofactors.


1998 ◽  
Vol 47 (4) ◽  
pp. 324-331 ◽  
Author(s):  
Grabbe ◽  
Welker ◽  
Grützkau ◽  
Dippel ◽  
Nürnberg ◽  
...  

2014 ◽  
Vol 192 (10) ◽  
pp. 4859-4866 ◽  
Author(s):  
Namit Sharma ◽  
Stephanie Everingham ◽  
Baskar Ramdas ◽  
Reuben Kapur ◽  
Andrew W. B. Craig

2017 ◽  
Vol 48 ◽  
pp. 1-7 ◽  
Author(s):  
Sun-Young Nam ◽  
Hee-Yun Kim ◽  
Hyung-Min Kim ◽  
Hyun-Ja Jeong

1992 ◽  
Vol 175 (1) ◽  
pp. 245-255 ◽  
Author(s):  
B K Wershil ◽  
M Tsai ◽  
E N Geissler ◽  
K M Zsebo ◽  
S J Galli

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.


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