Downstream signals initiated in mast cells by FcεRI and other receptors

Beaven, Michael A.; Baumgartner, Rudolf

doi:10.1016/s0952-7915(96)80002-1

Cited by 90 publications

(58 citation statements)

References 62 publications

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“…To further delineate the mechanism of action of the FD on nonIgE-mediated degranulation we examined Western blotting using antibodies to the phosphorylation-dependent activated forms of LAT and ERK1/ERK2 [26,27]. As seen in figure 5A neither Biotin or TTA significantly affected A23187-induced changes in MAPK or LAT.…”

Section: The Effect Of Fd On Non-ige Mediated Signaling Pathway Intermentioning

confidence: 99%

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Dellinger¹,

Brooks

Plunkett

et al. 2012

J Nanomedic Nanotechnol

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Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FcεRI). However, these cells can also be stimulated by other non-allergic secretagogues to release their inflammatory mediators. Certain fullerene derivatives (FD) have already been shown to stabilize FcεRI-mediated MC/PBB responses, but it is not know if they also stabilize these cells through non-IgEmediated mechanisms. A panel of FD was synthesized and tested for their ability to inhibit non-FcεRI mediated release from human MC and PBB. It was found that specifically engineered FD could significantly inhibit calcium ionophore, compound 48/80, somatostatin, and poly L-lysine induced MC degranulation and cytokine production, as well as blunt degranulation and cytokine production from N-formyl-methionine-leucine-phenylalanine (fMLP), poly L-lysine, and calcium ionophore stimulated PBB. The mechanism of inhibition was due in part to the prevention of secretagogueinduced increases in cellular reactive oxygen species (ROS) and calcium levels as well as the reduced activation of the MAPK signaling intermediates ERK1/ERK2 and LAT. Additionally, preincubation of MC with FD blunted the prostaglandin D 2 (PGD 2 ) production upon exposure to inflammatory stimuli. In both cell types, the extent of inhibition of mediator release in response to each secretagogue was dependent on the moieties/side chains attached to the carbon cage. These results further extend the utility of fullerene nanomaterials to control mediator release through non-IgE mediated pathways in MC/PBB.

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Section: The Effect Of Fd On Non-ige Mediated Signaling Pathway Intermentioning

confidence: 99%

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Dellinger¹,

Brooks

Plunkett

et al. 2012

J Nanomedic Nanotechnol

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“…This cell line provides a suitable model of signaling associated to functional responses triggered through a variety of receptors (23,25,30,31). Fig.…”

Section: Functional Interchangeability Of the Cy And Lectin Domains Omentioning

confidence: 99%

“…The rise of [Ca 2ϩ ] i in mast cells is associated to their degranulation, with serotonin release, and synthesis of cytokines, including TNF-␣ (23,25,31). We found that activation of protein kinase C and crosslinking of the stimulating mAb were required for optimal serotonin release (not shown).…”

Section: Different Activation Pathways Are Promoted By the Cy Domainsmentioning

confidence: 99%

“…To address this point, a series of chimeric molecules was constructed in which the CRD, N, or TM-Cy domains were exchanged. The RBL-2H3 rat mucosal mast cell line expressing these CD69/CD23 chimeric proteins was used as a model of mast cell activation (23) to study the structure-function relationship of these C-type lectins. Our results revealed the interchangeability between defined structural domains of these two proteins in terms of Ca 2ϩ fluxes, serotonin release, and TNF-␣ synthesis.…”

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confidence: 99%

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Functional Analysis of Ligand-Binding and Signal Transduction Domains of CD69 and CD23 C-Type Lectin Leukocyte Receptors

Sancho

Santis

Alonso-Lebrero

et al. 2000

The Journal of Immunology

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CD69 and CD23 are leukocyte receptors with distinctive pattern of cell expression and functional features that belong to different C-type lectin receptor subfamilies. To assess the functional equivalence of different domains of these structurally related proteins, a series of CD69/CD23 chimeras exchanging the carbohydrate recognition domain, the neck region, and the transmembrane and cytoplasmic domains were generated. Biochemical analysis revealed the importance of the neck region (Cys68) in the dimerization of CD69. Functional analysis of these chimeras in RBL-2H3 mast cells and Jurkat T cell lines showed the interchangeability of structural domains of both proteins regarding Ca2+ fluxes, serotonin release, and TNF-α synthesis. The type of the signal transduced mainly relied on the cytoplasmic domain and was independent of receptor oligomerization. The cytoplasmic domain of CD69 transduced a Ca2+-mediated signaling that was dependent on the extracellular uptake of Ca2+. Furthermore, a significant production of TNF-α was induced through the cytoplasmic domain of CD69 in RBL-2H3 cells, which was additive to that promoted via FcεRI, thus suggesting a role for CD69 in the late phase of reactions mediated by mast cells. Our results provide new important data on the functional equivalence of homologous domains of these two leukocyte receptors.

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“…This activation of Fc⑀RI induces histamine release following the activation of tyrosine kinases (Lyn, Syk, Btk, etc. ), phosphatidylinositol 3-kinase (PI3-K) (11)(12)(13)(14), and calcium increase (15). Although G protein-coupled receptor-mediated activation of PI3-K was also found in fMLP-stimulated human neutrophils and thrombin-stimulated human platelets (16 -19), the physiological role of PI3-K in these cells and its relation to calcium increase are somewhat uncertain.…”

mentioning

confidence: 99%

Requirement of Phosphatidylinositol 3-Kinase Activation and Calcium Influx for Leukotriene B4-induced Enzyme Release

Ito¹,

Yokomizo²,

Sasaki³

et al. 2002

Journal of Biological Chemistry

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Leukotriene B 4 (LTB 4 ) is a potent lipid mediator involved in host defense and inflammatory responses. It causes chemotaxis, generation of reactive oxygen species, and degranulation. However, only little is known of the molecular mechanisms by which LTB 4 induces these biological activities. To analyze the intracellular signaling pathways to mediate lysosomal enzyme release through the cloned LTB 4 receptor (BLT1), we transfected BLT1 to rat basophilic leukemia cells (RBL-2H3). LTB 4 dose-dependently released ␤-hexosaminidase, and the release was mostly inhibited when the cells were pretreated with pertussis toxin, indicating that the degranulation is mediated by G i proteins. LTB 4 activated phosphatidylinositol 3-kinase (PI3-K) through G i , and inhibition of PI3-K by wortmannin or LY290042 inhibited degranulation. Granulocytes from PI3-K␥-deficient mice showed reduced LTB 4 -induced degranulation, suggesting that this isozyme of PI3-K is involved in the degranulation. LTB 4 also caused calcium release from intracellular stores and calcium influx from the outside milieu through G i , but only the calcium influx is critical for the lysosomal enzyme release. Calcium influx and PI3-K activation are both downstream events of G i , since they were inhibited by pertussis toxin. These two events are in essence independent each other, because calcium depletion did not affect PI3-K, and inhibition of PI3-K did not attenuate calcium influx significantly. Thus, our results have clearly shown that LTB 4 binds BLT1 and activates G i -like protein, and both PI3-K␥ activation and a sustained calcium elevation by calcium influx are necessary for enzyme release in these cells.Leukotreine B 4 (LTB 4 ), 1 a metabolite of arachidonic acid, is one of the most potent chemoattractants for neutrophils. LTB 4 activates leukocytes, leading to chemotaxis, release of lysosomal enzyme, and production of superoxide anions, thus playing important roles in host defense (1, 2). Overproduction of LTB 4 is involved in various inflammatory diseases including psoriasis (3), bronchial asthma (4), rheumatoid arthritis (5), inflammatory bowel diseases (6), and ischemic renal failure (7). LTB 4 binds to a specific G protein-coupled receptor named BLT1, which was cloned in our laboratory (8). Signaling to activate leukocytes through BLT1 is poorly understood, in part because most of the previous studies have been done using peripheral leukocytes, especially granulocytes. The lifetime of these cells is short (several days), which makes it difficult to perform studies using various drugs or gene transfection. We have previously analyzed signaling pathway from BLT1 using Chinese hamster ovary cells stably expressing human BLT1 (8). In these cells, LTB 4 increases intracellular IP3 levels by G q -like protein(s), inhibits adenylyl cyclase activity, and activates chemotaxis through G i -like protein(s). In hematopoietic cells, however, the intracellular events leading to release of lysosomal enzymes and generation of oxygen species are poorly understood....

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Downstream signals initiated in mast cells by FcεRI and other receptors

Cited by 90 publications

References 62 publications

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Functional Analysis of Ligand-Binding and Signal Transduction Domains of CD69 and CD23 C-Type Lectin Leukocyte Receptors

Requirement of Phosphatidylinositol 3-Kinase Activation and Calcium Influx for Leukotriene B4-induced Enzyme Release

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