A Comparative Study of the FcεRI Molecule on Human Mast Cell and Basophil Cell Lines

2005 ◽  
Vol 137 (2) ◽  
pp. 93-103 ◽  
Author(s):  
B.M. Jensen ◽  
S. Dissing ◽  
P.S. Skov ◽  
L.K. Poulsen
Keyword(s):  
Mast Cell ◽  
Comparative Study ◽  
Cell Lines ◽  
Human Mast Cell ◽  
Basophil Cell

277 Human mast cell and basophil cell lines produce interleukin 8 and 6

1991 ◽  
Vol 87 (1) ◽  
pp. 209 ◽  
Author(s):  
A MOLLER ◽  
D SCHADENDORF ◽  
U LIPPERT ◽  
E FORSTER ◽  
T LUGER ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Lines ◽  
Interleukin 8 ◽  
Human Mast Cell ◽  
Basophil Cell

EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 315-322 ◽  
Author(s):  
Jingxuan Pan ◽  
Alfonso Quintás-Cardama ◽  
Hagop M. Kantarjian ◽  
Cem Akin ◽  
Taghi Manshouri ◽  
...  
Keyword(s):  
Mast Cell ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Human Mast Cell ◽  
Activation Loop ◽  
Dependent Manner ◽  
Juxtamembrane Domain ◽  
Dose Dependent

Abstract Gain-of-function mutations of the receptor tyrosine kinase KIT play a key role in the pathogenesis of systemic mastocytosis (SM), gastrointestinal stromal tumors (GISTs), and some cases of acute myeloid leukemia (AML). Whereas KIT juxtamembrane domain mutations seen in most patients with GIST are highly sensitive to imatinib, the kinase activation loop mutant D816V, frequently encountered in SM, hampers the binding ability of imatinib. We investigated the inhibitory activity of the novel tyrosine kinase inhibitor EXEL-0862 against 2 subclones of human mast cell line-1 (HMC-1)—HMC-1.1, harboring the juxtamembrane domain mutation V560G, and HMC-1.2, carrying V560G and the activation loop mutation D816V, found in more than 80% of patients with SM. EXEL-0862 inhibited the phosphorylation of KIT in a dose-dependent manner and decreased cell proliferation in both mast cell lines with higher activity against HMC-1.2 cells. The phosphorylation of KIT-dependent signal transducer and activator of transcription-3 (STAT3) and STAT5 was abrogated upon exposure to nanomolar concentrations of EXEL-0862. In addition, EXEL-0862 induced a time- and dose-dependent proapoptotic effect in both mast cell lines and caused a significant reduction in mast-cell content in bone marrow samples from patients with SM harboring D816V and from those without the D816V mutation. We conclude that EXEL-0862 is active against KIT activation loop mutants and is a promising candidate for the treatment of patients with SM and other KIT-driven malignancies harboring active site mutations.

scholarly journals Description and Characterization of a Novel Human Mast Cell Line for Scientific Study

2019 ◽  
Vol 20 (22) ◽  
pp. 5520 ◽  
Author(s):  
Arnold S. Kirshenbaum ◽  
Yuzhi Yin ◽  
J. Bruce Sundstrom ◽  
Geethani Bandara ◽  
Dean D. Metcalfe
Keyword(s):  
Gene Expression ◽  
Mast Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cell Biology ◽  
Preclinical Study ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Cytokine Signaling ◽  
Surface Receptor

Background: Laboratory of allergic diseases 2 (LAD2) human mast cells were developed over 15 years ago and have been distributed worldwide for studying mast cell proliferation, receptor expression, mediator release/inhibition, and signaling. LAD2 cells were derived from CD34+ cells following marrow aspiration of a patient with aggressive mastocytosis with no identified mutations in KIT. Another aspiration gave rise to a second cell line which has recently been re-established (LADR). We queried whether LADR had unique properties for the preclinical study of human mast cell biology. Methods: LADR and LAD2 cells were cultured under identical conditions. Experiments examined proliferation, beta-hexosaminidase (β-hex) release, surface receptor and granular protease expression, infectivity with HIV, and gene expression. Results: LADR cells were larger and more granulated as seen with Wright–Giemsa staining and flow cytometry, with cell numbers doubling in 4 weeks, in contrast to LAD2 cells, which doubled every 2 weeks. Both LADR and LAD2 cells released granular contents following aggregation of FcεRI. LADR cells showed log-fold increases in FcεRI/CD117 and expressed CD13, CD33, CD34, CD63, CD117, CD123, CD133, CD184, CD193, and CD195, while LAD2 cells expressed CD33, CD34, CD63, CD117, CD133, CD193 but not CD13, CD123, CD184, or CD195. LADR tryptase expression was one-log-fold increased. LADR cell and LAD2 cell chymase expression were similar. Both cell lines could be infected with T-tropic, M-tropic, and dual tropic HIV. Following monomeric human IgE stimulation, LADR cells showed greater surface receptor and mRNA expression for CD184 and CD195. Expression arrays revealed differences in gene upregulation, especially for the suppressor of cytokine signaling (SOCS) family of genes with their role in JAK2/STAT3 signaling and cellular myelocytomatosis oncogene (c-MYC) in cell growth and regulation. Conclusions: LADR cells are thus unique in that they exhibit a slower proliferation rate, are more advanced in development, have increased FcεRI/CD117 and tryptase expression, have a different profile of gene expression, and show earlier infectivity with HIV-BAL, LAV, and TYBE when compared to LAD2 cells. This new cell line is thus a valuable addition to the few FcεRI+ human mast cell lines previously described and available for scientific inquiry.

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