Demonstration of mast-cell chemotactic activity in nasal lavage fluid: characterization of one chemotaxin as c-kit ligand, stem cell factor

Allergy ◽  
1998 ◽  
Vol 53 (9) ◽  
pp. 874-879 ◽  
Author(s):  
G. Nilsson ◽  
M. Hjertson ◽  
M. Andersson ◽  
L. Greiff ◽  
C. Svensson ◽  
...  
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.


1996 ◽  
Vol 183 (6) ◽  
pp. 2681-2686 ◽  
Author(s):  
J J Costa ◽  
G D Demetri ◽  
T J Harrist ◽  
A M Dvorak ◽  
D F Hayes ◽  
...  

Stem cell factor (SCF), also known as mast cell growth factor, kit ligand, and steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 micrograms/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course of r-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell alpha-tryptase. Five subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes.


2020 ◽  
Vol 145 (2) ◽  
pp. AB170
Author(s):  
Toru Takahashi ◽  
Atsushi Kato ◽  
Lydia Suh ◽  
Roderick Carter ◽  
Kathleen Harris ◽  
...  

2011 ◽  
Vol 127 (3) ◽  
pp. 815-822.e5 ◽  
Author(s):  
Tanya M. Laidlaw ◽  
John W. Steinke ◽  
Adrienne M. Tiñana ◽  
Chunli Feng ◽  
Wei Xing ◽  
...  

1991 ◽  
Vol 88 (14) ◽  
pp. 6382-6386 ◽  
Author(s):  
M. Tsai ◽  
T. Takeishi ◽  
H. Thompson ◽  
K. E. Langley ◽  
K. M. Zsebo ◽  
...  

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