scholarly journals c-kit ligand: a unique potentiator of mediator release by human lung mast cells.

1992 ◽  
Vol 175 (1) ◽  
pp. 237-244 ◽  
Author(s):  
S C Bischoff ◽  
C A Dahinden
Keyword(s):  
Growth Factor ◽  
Mast Cells ◽  
Cell Growth ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Mediator Release ◽  
Ige Receptor ◽  
Effector Cells ◽  
Promote Cell Proliferation ◽  
Kit Ligand

Mast cells (MC) play a central role in extrinsic allergic reactions such as asthma and may participate in other inflammatory and fibrotic processes. However, with the exception of immunoglobulin E (IgE) receptor-dependent stimulation, no secretagogues of human lung MC have yet been described. It is also unclear whether mediator release can be regulated by certain cytokines as demonstrated previously in basophils and other human inflammatory effector cells. Here, we show that the c-kit ligand (KL), a recently identified stem cell growth factor, at concentrations 10-100 times lower than that required to promote cell proliferation, enhances the release of histamine and leukotriene C4 in response to IgE receptor crosslinking of human lung MC. KL does not induce mediator release per se, but increases the sensitivity of MC to anti-IgE receptor stimulation and also enhances mediator release to maximally effective concentrations of anti-IgE receptor antibody. By contrast, a large number of cytokines examined, including the mast cell growth factors/agonists in rodents, interleukin 3 (IL-3), IL-4, IL-9, and nerve growth factor, were ineffective in this respect. These findings suggest a unique role of KL in regulating effector functions of human mucosal MC.

Mast Cell Heterogeneity in Human Lung Tissue

1989 ◽  
Vol 77 (3) ◽  
pp. 297-304 ◽  
Author(s):  
F. J. Van Overveld ◽  
L. A. M. J. Houben ◽  
F. E. M. Schmitz du Moulin ◽  
P. L. B. Bruijnzeel ◽  
J. A. M. Raaijmakers ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Alcian Blue ◽  
Lung Tissue ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Human Lung Tissue ◽  
No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

scholarly journals Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation

1993 ◽  
Vol 268 (20) ◽  
pp. 14881-14887
Author(s):  
K. Horigome ◽  
J.C. Pryor ◽  
E.D. Bullock ◽  
E.M. Johnson
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Mast Cells ◽  
Mediator Release ◽  
Nerve Growth

scholarly journals Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4322-4332 ◽  
Author(s):  
P Valent ◽  
E Spanblochl ◽  
HC Bankl ◽  
WR Sperr ◽  
C Marosi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Growth Factor ◽  
Mast Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Kit Ligand ◽  
Mast Cell Growth Factor

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.

scholarly journals CD203c is Overexpressed on Neoplastic Mast Cells in Systemic Mastocytosis and is Upregulated upon IgE Receptor Cross-Linking

2008 ◽  
Vol 21 (4) ◽  
pp. 797-806 ◽  
Author(s):  
A.W. Hauswirth ◽  
L. Escribano ◽  
A. Prados ◽  
R. Nuñez ◽  
I. Mirkina ◽  
...  
Keyword(s):  
Mast Cells ◽  
Surface Antigen ◽  
Systemic Mastocytosis ◽  
Mrna Level ◽  
Surface Expression ◽  
Pcr Analysis ◽  
Cross Linking ◽  
Ige Receptor ◽  
Kit Ligand ◽  
Mast Cell Leukemia

The ectoenzyme E-NPP3 (CD203c) has recently been identified as a novel activation-linked cell surface antigen on basophils. In the present study, we examined expression of CD203c on normal mast cells (MC) and bone marrow (bm) MC derived from 85 patients with systemic mastocytosis (SM), including cases with indolent SM (ISM, n=72), SM with associated clonal hematologic non-MC-lineage disease (SM-AHNMD, n=6), aggressive SM (ASM, n=3), and mast cell leukemia (MCL, n=4). Surface expression of CD203c was analyzed by multicolor flow cytometry. In patients with SM, bm MC expressed significantly higher amounts of CD203c compared to normal bm MC (median MFI in controls: 260 versus median MFI in SM: 516, p<0.05). Slightly lower amounts of CD203c were detected on MC in SM-AHNMD and ASM compared to ISM. To demonstrate CD203c expression in MC at the mRNA level, neoplastic MC were highly enriched by cell sorting, and were found to express CD203c mRNA in RT-PCR analysis. Cross-linking of the IgE receptor on MC resulted in a substantial upregulation of CD203c, whereas the KIT-ligand stem cell factor (SCF) showed no significant effects. In conclusion, CD203c is a novel activation-linked surface antigen on MC that is upregulated in response to IgE receptor cross-linking and is overexpressed on neoplastic MC in patients with SM.

scholarly journals Angiogenic factors stimulate mast-cell migration

Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2488-2493 ◽  
Author(s):  
BL Gruber ◽  
MJ Marchese ◽  
R Kew
Keyword(s):  
Mast Cell ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Mast Cells ◽  
Cell Growth ◽  
Chemotactic Factor ◽  
Angiogenic Factor ◽  
Directed Migration ◽  
Endothelial Cell Growth Factor ◽  
Endothelial Cell Growth

Abstract Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell-shaped dose-response curve. Another potent angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase-inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.

scholarly journals Mast Cells as a Potential Prognostic Marker in Prostate Cancer

2013 ◽  
Vol 35 ◽  
pp. 711-720 ◽  
Author(s):  
Gianluigi Taverna ◽  
Guido Giusti ◽  
Mauro Seveso ◽  
Rodolfo Hurle ◽  
Piergiuseppe Colombo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Effector Cells ◽  
Host Interactions ◽  
Adaptive Immune Cells ◽  
Primary Prostate Cancer ◽  
Intensive Investigation

Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men’s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs), infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.

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