scholarly journals Leukocyte common antigen (CD45) is required for immunoglobulin E-mediated degranulation of mast cells.

1994 ◽  
Vol 180 (2) ◽  
pp. 471-476 ◽  
Author(s):  
S A Berger ◽  
T W Mak ◽  
C J Paige
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Tyrosine Phosphatase ◽  
Cross Linking ◽  
Ionophore A23187 ◽  
Wild Type ◽  
Ige Receptor ◽  
High Affinity ◽  
Deficient Mice

We demonstrate using primary mast cell cultures derived from wild-type and CD45-deficient mice that mast cell triggering through the high-affinity immunoglobulin E (IgE) receptor requires the cell surface tyrosine phosphatase CD45. Unlike wild-type cells, cross-linking of surface-bound IgE in mast cells deficient in CD45 does not induce degranulation. Degranulation in these mutant cells does occur after treatment with the calcium ionophore A23187 indicating that the degranulation machinery is intact in these cells. We also demonstrate that the tyrosine phosphatase inhibitors orthoVanadate and perVanadate inhibit degranulation in wild-type mast cells, as does cross-linking of CD45 by anti-CD45 antibodies. Finally, we show that CD45-deficient mice are resistant to IgE-dependent systemic anaphylaxis. These results show that, like the T cell receptor and the antigen receptor on B cells, there is an absolute requirement for CD45 in signaling via the high affinity IgE receptor, expanding the number of receptors for which CD45 is an essential component.

scholarly journals The emerging role of mast cell proteases in asthma

2019 ◽  
Vol 54 (4) ◽  
pp. 1900685 ◽  
Author(s):  
Gunnar Pejler
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Current Knowledge ◽  
Secretory Granules ◽  
Cross Linking ◽  
Lysosomal Hydrolases ◽  
Ige Receptor ◽  
Deficient Mice ◽  
Lines Of Evidence

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

Immunologic mast cell-mediated responses and histamine release are attenuated by heparin

1992 ◽  
Vol 73 (3) ◽  
pp. 1093-1101 ◽  
Author(s):  
J. Lucio ◽  
J. D'Brot ◽  
C. B. Guo ◽  
W. M. Abraham ◽  
L. M. Lichtenstein ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Calcium Ionophore ◽  
Intradermal Injection ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Dependent Manner

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin “partially” inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Mast cells lacking the high affinity immunoglobulin E receptor are deficient in Fc epsilon RI gamma messenger RNA.

1995 ◽  
Vol 182 (2) ◽  
pp. 567-574 ◽  
Author(s):  
J J Ryan ◽  
C A Kinzer ◽  
W E Paul
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Messenger Rna ◽  
Immunoglobulin E ◽  
Leukemia Virus ◽  
Molecular Defect ◽  
Gamma Chain ◽  
Stable Transfectants ◽  
High Affinity ◽  
Zeta Chain

A population of cells that express mast cell markers, including the membrane protein p161, but that lack expression of the high affinity IgE receptor, Fc epsilon RI, can be routinely grown from bone marrow. Ionomycin, but not IgE immune complexes, causes these cells to release serotonin and to express IL-3 and IL-13 mRNA, consistent with their being FC epsilon RI-deficient mast cells. These p161+/Fc epsilon RI- mast cells expressed normal amounts of Fc epsilon RI alpha and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA. In addition, this novel mast cell population expressed CD3 zeta chain mRNA, which p161+/Fc epsilon RI+ mast cells did not. CD3 zeta stable transfectants of Abelson-murine leukemia virus-transformed p161+/Fc epsilon RI+ mast cells continued to express Fc epsilon RI. This strongly suggests that the failure of p161+/Fc epsilon RI- mast cells to express IgE receptors was not caused by the presence of CD3 zeta chain. Transfection of human Fc epsilon RI gamma cDNA into p161+/Fc epsilon RI- mast cells rescued IgE binding. These stable transfectants released serotonin in response to cross-linkage of Fc epsilon RI, demonstrating that the molecular defect of p161+/Fc epsilon RI- mast cells is indeed the loss of Fc epsilon RI gamma expression.

scholarly journals Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.

1994 ◽  
Vol 14 (8) ◽  
pp. 5108-5113 ◽  
Author(s):  
Y Kawakami ◽  
L Yao ◽  
T Miura ◽  
S Tsukada ◽  
O N Witte ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Immunoglobulin E ◽  
Cross Linking ◽  
Mouse Bone Marrow ◽  
Ionophore A23187 ◽  
Membrane Compartment ◽  
High Affinity Receptor ◽  
Protein Kinase C Activation

Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co-immunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.

Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking

1994 ◽  
Vol 14 (8) ◽  
pp. 5108-5113
Author(s):  
Y Kawakami ◽  
L Yao ◽  
T Miura ◽  
S Tsukada ◽  
O N Witte ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Immunoglobulin E ◽  
Cross Linking ◽  
Mouse Bone Marrow ◽  
Ionophore A23187 ◽  
Membrane Compartment ◽  
High Affinity Receptor ◽  
Protein Kinase C Activation

Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co-immunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.

Amomum xanthiodes Inhibits Mast Cell-Mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production

2005 ◽  
Vol 230 (9) ◽  
pp. 681-687 ◽  
Author(s):  
Sang-Hyun Kim ◽  
Tae-Yong Shin
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Proinflammatory Cytokines ◽  
Immunoglobulin E ◽  
Ionophore A23187 ◽  
Allergic Reactions ◽  
Disodium Cromoglycate ◽  
Plasma Histamine ◽  
Intracellular Ca

In this study, we investigated the effect of Amomum xanthiodes (Zingiberaceae) extract (AXE) on the mast cell-mediated allergy model and studied the possible mechanism of action. We found that AXE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. Additionally, AXE decreased immunoglobulin E (IgE)-mediated local allergic reactions and passive cutaneous anaphylaxis (PCA), and AXE dose-dependently attenuated the release of histamine from rat peritoneal mast cells (RPMC) activated by compound 48/80 or IgE. The amounts of AXE needed for inhibition of compound 48/80-induced plasma histamine release and PCA were similar to disodium cromoglycate, the known anti-allergic drug. We found that AXE increased the cAMP levels and decreased the compound 48/80-induced intracellular Ca2+. Furthermore, AXE attenuated the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187)-stimulated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 secretion in human mast cells. The inhibitory effect of AXE on the proinflammatory cytokines was nuclear factor-κB (NF-κB)-dependent. In addition, AXE decreased PMA plus A23187-induced degradation of IκBα and the nuclear translocation of NF-κB. Our findings provide evidence that AXE inhibits mast cell-derived immediate-type allergic reactions, and that cAMP, intracellular Ca2+, proinflammatory cytokines, and NF-κB are involved in these effects.

scholarly journals Mast Cell Deficiency Protects Mice from Surgery-Induced Neuroinflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiang Zhang ◽  
Hongquan Dong ◽  
Fei Wang ◽  
Jun Zhang
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Neuronal Apoptosis ◽  
Microglial Activation ◽  
Tibial Fracture ◽  
Wild Type ◽  
The Brain ◽  
Fracture Surgery ◽  
Deficient Mice

Neuroinflammation plays a key role in the occurrence and development of neurodegenerative diseases. Microglia, the resident immune cells in the brain, have been recognized to contribute to neuroinflammation. Previous studies have shown that activated mast cells may be involved in surgery-induced neuroinflammation and neuronal apoptosis by using pharmacological methods. This study is aimed at ascertaining the exactly role of mast cells on neuroinflammation with the mast cell-deficient mice. Adult male C57BL6/J wild-type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tibial fracture surgery. Blood-brain barrier (BBB) breakdown, microglial activation, and neuroinflammatory levels were examined at 1 day after surgery. Surgery-induced BBB breakdown, microglial activation, and neuroinflammatory levels were significantly, pharmacologically reduced using a mast cell stabilizer, cromolyn sodium in WT mice (P<0.05). These results were reproduced with mast cell deficiency. WT mice administered intraventricularly with cromolyn exhibited reduced BBB breakdown, microglial activation, and neuroinflammatory levels versus vehicle (P<0.05). But there was no effect of cromolyn versus vehicle in Wsh mice, clarifying the specificity of cromolyn on brain mast cells. These findings demonstrated that activated mast cells promote surgery-induced BBB breakdown and neuroinflammation in mice, and open up a new therapeutic target for neuroinflammation-related diseases.

scholarly journals Partial Protection against Helicobacter pylori in the Absence of Mast Cells in Mice

2009 ◽  
Vol 77 (12) ◽  
pp. 5543-5550 ◽  
Author(s):  
Hua Ding ◽  
John G. Nedrud ◽  
Barry Wershil ◽  
Raymond W. Redline ◽  
Thomas G. Blanchard ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Mast Cell ◽  
Mast Cells ◽  
Bacterial Load ◽  
Interleukin 17 ◽  
Wild Type ◽  
Spleen Cells ◽  
Tnf Α ◽  
H Pylori ◽  
Deficient Mice

ABSTRACT The goal of this study is to evaluate the contribution of mast cells to Helicobacter pylori immunity in a model of vaccine-induced protection. Mast cell-deficient KitlSl /KitlSl-d and control mice were immunized with H. pylori sonicate plus cholera toxin and challenged with H. pylori, and the bacterial loads, inflammatory infiltrates, and cytokine responses were evaluated and compared at 1, 2, and 4 weeks postchallenge. In vitro stimulation assays were performed using bone marrow-derived mast cells, and recall assays were performed with spleen cells of immunized mast cell-deficient and wild-type mice. Bacterial clearance was observed by 2 weeks postchallenge in mast cell-deficient mice. The bacterial load was reduced by 4.0 log CFU in wild-type mice and by 1.5 log CFU in mast cell-deficient mice. Neutrophil numbers in the gastric mucosa of immune KitlSl /KitlSl-d mice were lower than those for immune wild-type mice (P < 0.05). Levels of gastric interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) were also significantly lower in immune KitlSl /KitlSl-d mice than in wild-type mice (P < 0.001). Immunized mast cell-deficient and wild-type mouse spleen cells produced IFN-γ and IL-17 in response to H. pylori antigen stimulation. TNF-α and CXC chemokines were detected in mast cell supernatants after 24 h of stimulation with H. pylori antigen. The results indicate that mast cells are not essential for but do contribute to vaccine-induced immunity and that mast cells contribute to neutrophil recruitment and inflammation in response to H. pylori.

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