11 results on '"Inositol 1,4,5-Trisphosphate immunology"'
Search Results
2. Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells.
- Author
-
Croisier H, Tan X, Chen J, Sneyd J, Sanderson MJ, and Brook BS
- Subjects
- Animals, Calcium immunology, Calcium metabolism, Calcium Signaling, Cell Proliferation drug effects, Computer Simulation, Female, Gene Expression Regulation, Immunization, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate metabolism, Inositol 1,4,5-Trisphosphate Receptors genetics, Inositol 1,4,5-Trisphosphate Receptors immunology, Ion Channel Gating drug effects, Kinetics, Lung drug effects, Lung immunology, Lung pathology, Mice, Mice, Inbred BALB C, Microtomy, Models, Statistical, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle pathology, Respiratory Hypersensitivity chemically induced, Respiratory Hypersensitivity genetics, Respiratory Hypersensitivity pathology, Respiratory Mucosa drug effects, Respiratory Mucosa immunology, Respiratory Mucosa pathology, Ryanodine Receptor Calcium Release Channel genetics, Tissue Culture Techniques, Caffeine pharmacology, Immunologic Factors pharmacology, Myocytes, Smooth Muscle immunology, Respiratory Hypersensitivity immunology, Ryanodine Receptor Calcium Release Channel immunology
- Abstract
Intracellular Ca(2+) dynamics of airway smooth muscle cells (ASMCs) are believed to play a major role in airway hyperresponsiveness and remodeling in asthma. Prior studies have underscored a prominent role for inositol 1,4,5-triphosphate (IP3) receptors in normal agonist-induced Ca(2+) oscillations, whereas ryanodine receptors (RyRs) appear to remain closed during such Ca(2+) oscillations, which mediate ASMC contraction. Nevertheless, RyRs have been hypothesized to play a role in hyperresponsive Ca(2+) signaling. This could be explained by RyRs being "sensitized" to open more frequently by certain compounds. We investigate the implications of RyR sensitization on Ca(2+) dynamics in ASMC using a combination of mathematical modeling and experiments with mouse precision-cut lung slices. Caffeine is used to increase the sensitivity of RyRs to cytosolic Ca(2+) concentration ([Ca(2+)]i) and sarcoplasmic reticulum Ca(2+) ([Ca(2+)]SR). In ASMCs, high caffeine concentrations (>10 mM) induce a sustained elevation of [Ca(2+)]i. Our mathematical model accounts for this by the activation of store-operated Ca(2+) entry that results from a large increase in the RyR sensitivity to [Ca(2+)]SR and the associated Ca(2+) release, which leads to a reduction of [Ca(2+)]SR. Importantly, our model also predicts that: (1) moderate RyR sensitization induces slow Ca(2+) oscillations, a result experimentally confirmed with low concentrations of caffeine; and (2) high RyR sensitization suppresses fast, agonist-induced Ca(2+) oscillations by inducing substantial store-operated Ca(2+) entry and elevated [Ca(2+)]i. These results suggest that RyR sensitization could play a role in ASMC proliferation (by inducing slow Ca(2+) oscillations) and in airway hyperresponsiveness (by inducing greater mean [Ca(2+)]i for similar levels of contractile agonist).
- Published
- 2015
- Full Text
- View/download PDF
3. Phospholipase Cγ-2 and intracellular calcium are required for lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon regulatory factor 3 (IRF3) activation.
- Author
-
Chiang CY, Veckman V, Limmer K, and David M
- Subjects
- Animals, Calcium immunology, Calcium Signaling physiology, Cell Line, Endocytosis physiology, Immunity, Innate drug effects, Immunity, Innate physiology, Inositol 1,4,5-Trisphosphate genetics, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate metabolism, Interferon Regulatory Factor-3 genetics, Interferon Regulatory Factor-3 immunology, Macrophages cytology, Macrophages immunology, Mice, Phospholipase C gamma genetics, Phospholipase C gamma immunology, Protein Transport drug effects, Protein Transport physiology, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 immunology, Calcium metabolism, Calcium Signaling drug effects, Endocytosis drug effects, Interferon Regulatory Factor-3 metabolism, Lipopolysaccharides pharmacology, Macrophages metabolism, Phospholipase C gamma metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Toll-like receptor 4 (TLR4) is unique among the TLRs in its use of multiple adaptor proteins leading to activation of both the interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) pathways. Previous work has demonstrated that TLR4 initiates NF-κB activation from the plasma membrane, but that subsequent TLR4 translocation to the endosomes is required for IRF3 activation. Here we have characterized several components of the signaling pathway that governs TLR4 translocation and subsequent IRF3 activation. We find that phospholipase C γ2 (PLCγ2) accounts for LPS-induced inositol 1,4,5-trisphosphate (IP(3)) production and subsequent calcium (Ca(2+)) release. Blockage of PLCγ2 function by inhibitors or knockdown of PLCγ2 expression by siRNAs in RAW 264.7 macrophages lead to reduced IRF3, but enhanced NF-κB activation. In addition, bone marrow-derived macrophages from PLCγ2-deficient mice showed impaired IRF3 phosphorylation and expression of IRF3-regulated genes after LPS stimulation. Using cell fractionation, we show that PLCγ2-IP(3)-Ca(2+) signaling cascade is required for TLR4 endocytosis following LPS stimulation. In conclusion, our results describe a novel role of the PLCγ2-IP(3)-Ca(2+) cascade in the LPS-induced innate immune response pathway where release of intracellular Ca(2+) mediates TLR4 trafficking and subsequent activation of IRF3.
- Published
- 2012
- Full Text
- View/download PDF
4. Regulation of phospholipase C-gamma2 networks in B lymphocytes.
- Author
-
Hikida M and Kurosaki T
- Subjects
- Allosteric Regulation, Animals, B-Lymphocytes immunology, Calcium immunology, Calcium Channels immunology, Calcium Channels metabolism, Endoplasmic Reticulum immunology, Endoplasmic Reticulum metabolism, Humans, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate metabolism, Inositol 1,4,5-Trisphosphate Receptors genetics, Inositol 1,4,5-Trisphosphate Receptors immunology, NFATC Transcription Factors genetics, NFATC Transcription Factors immunology, Phospholipase C gamma genetics, Phospholipase C gamma immunology, Protein Transport immunology, Receptors, Antigen, B-Cell immunology, Receptors, Antigen, B-Cell metabolism, Signal Transduction immunology, Transcriptional Activation immunology, B-Lymphocytes metabolism, Calcium metabolism, Inositol 1,4,5-Trisphosphate Receptors metabolism, NFATC Transcription Factors metabolism, Phospholipase C gamma metabolism
- Abstract
The modulation of inositol-1,4,5-trisphosphate (IP3), a product of phospholipase C (PLC) activity, is one of a common signaling mechanism used in many biological systems. B lymphocytes also rely on IP3 and subsequent calcium signaling to ensure appropriate developmental outcomes, as well as antigen-specific responses. In establishing the optimal intensity and duration of the PLC-gamma activity, an important role has emerged for adaptor molecules, which direct the appropriate subcellular localization of PLC-gamma and induce its conformational changes. Generated IP3 binds to IP3 receptors located on the endoplasmic reticulum (ER), which in turn is essential for triggering calcium release from the ER and subsequent entry of extracellular calcium by so-called Ca2+ entry channels. Recent data has begun to shed new light on the connection between the calcium release and the influx of extracellular calcium, and the molecular identity of the Ca2+ entry channels.
- Published
- 2005
- Full Text
- View/download PDF
5. Calcium channels in lymphocytes.
- Author
-
Grafton G and Thwaite L
- Subjects
- Humans, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate Receptors, NADP immunology, Receptors, Cytoplasmic and Nuclear immunology, Receptors, Immunologic immunology, Ryanodine Receptor Calcium Release Channel immunology, Calcium Channels immunology, Lymphocyte Subsets immunology, NADP analogs & derivatives
- Published
- 2001
- Full Text
- View/download PDF
6. The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells.
- Author
-
Hederer RA, Guntermann C, Miller N, Nagy P, Szollosi J, Damjanovich S, Hale G, and Alexander DR
- Subjects
- Alemtuzumab, Antibodies, Monoclonal, Humanized, Antigens, CD metabolism, CD52 Antigen, Calcium physiology, Calcium Signaling immunology, Cells, Cultured, Glycoproteins metabolism, Humans, Inositol 1,4,5-Trisphosphate immunology, Isoenzymes immunology, Jurkat Cells, Phospholipase C gamma, Receptors, Antigen, T-Cell metabolism, Signal Transduction genetics, T-Lymphocytes metabolism, Transfection, Type C Phospholipases immunology, Antibodies, Monoclonal physiology, Antibodies, Neoplasm physiology, Antigens, CD physiology, Antigens, Neoplasm, Glycoproteins physiology, Leukocyte Common Antigens physiology, Receptors, Antigen, T-Cell physiology, Signal Transduction immunology, T-Lymphocytes enzymology, T-Lymphocytes immunology
- Abstract
Campath-1H, a humanized mAb undergoing clinical trials for treatment of leukemia, transplantation and autoimmune diseases, produces substantial lymphocyte depletion in vivo. The antibody binds to CD52, a highly glycosylated molecule attached to the membrane by a glycosylphosphatidylinositol anchor. Cross-linked Campath-1H is known to activate T cells in vitro. We have investigated the molecular basis for these effects by comparing the protein tyrosine phosphorylation signals induced by Campath-1H and the CD3 mAb OKT3 in primary T cells, and in CD45(+)TCR(+), CD45(-)TCR(+) and CD45(+)TCR(-) Jurkat subclones transfected with CD52. Our results show that Campath-1H triggers similar tyrosine phosphorylation events as OKT3 in both primary T cells and in the CD45(+)TCR(+) Jurkat sub-clone, albeit at quantitatively lower levels. However, no phospholipase C gamma 1 activation nor calcium signals were detected in response to CD52 ligation. The CD52-mediated induction of protein tyrosine phosphorylation was absolutely dependent upon the expression of both the TCR and the CD45 phosphotyrosine phosphatase at the cell surface. Cross-linking of Campath-1H was essential for signal transduction in all cells investigated. Fluorescence resonance energy transfer was used to demonstrate CD52 homo-association at the cell surface in Jurkat T cells in a TCR- and CD45-independent manner, and CD52-TCR association in CD45(+)TCR(+) cells. We propose a model to explain the activating effects of Campath-1H in which CD52 mAb cross-linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface, thereby inducing signals via the TCR by a process which depends on the CD45-mediated regulation of the p56(lck) and p59(fyn) tyrosine kinases.
- Published
- 2000
- Full Text
- View/download PDF
7. Localization of inositol 1,4,5-trisphosphate receptors in the rat kidney.
- Author
-
Monkawa T, Hayashi M, Miyawaki A, Sugiyama T, Yamamoto-Hino M, Hasegawa M, Furuichi T, Mikoshiba K, and Saruta T
- Subjects
- Animals, Antibodies, Monoclonal, Calcium Channels immunology, Glomerular Mesangium blood supply, Immunohistochemistry, Inositol 1,4,5-Trisphosphate analysis, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate Receptors, Kidney Cortex blood supply, Male, Mice, Muscle, Smooth, Vascular chemistry, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear immunology, Calcium Channels analysis, Glomerular Mesangium chemistry, Kidney Cortex chemistry, Kidney Tubules, Collecting chemistry, Receptors, Cytoplasmic and Nuclear analysis
- Abstract
Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) serve as intracellular calcium release channels involved in signal transduction of various hormones in the kidney. Molecular cloning studies have shown that there are three types of IP3R, designated type 1, type 2, and type 3. To characterize their localizations in the rat kidney, we employed immunohistochemical studies using type-specific monoclonal antibodies that were raised against the 15 C-terminal amino acids of each type of IP3R. Type 1 was detected in glomerular mesangial cells and vascular smooth muscle cells. Type 2 was expressed exclusively in intercalated cells of collecting ducts from the cortex to the inner medulla. Type 3 was expressed in vascular smooth muscle cells, glomerular mesangial cells, and some cells of cortical collecting ducts, probably principal cells. As to the subcellular distribution, type 1 and type 2 showed a homogenous distribution in the cytoplasm, whereas type 3 was present mainly in the basolateral portion of the cytoplasm. These results indicate that IP3R isoforms were expressed in a cell-specific manner. The heterogeneous subcellular localizations among the IP3R types suggests compartmentalization of distinct IP3-sensitive Ca2+ pools.
- Published
- 1998
- Full Text
- View/download PDF
8. Comparison of type 2 inositol 1,4,5-trisphosphate receptor distribution and subcellular Ca2+ release sites that support Ca2+ waves in cultured astrocytes.
- Author
-
Sheppard CA, Simpson PB, Sharp AH, Nucifora FC, Ross CA, Lange GD, and Russell JT
- Subjects
- Animals, Astrocytes cytology, Blotting, Western, Calcium Channels drug effects, Calcium Channels immunology, Cells, Cultured, Cerebral Cortex cytology, Endoplasmic Reticulum chemistry, Endoplasmic Reticulum metabolism, Fluorescent Antibody Technique, Indirect, Glial Fibrillary Acidic Protein analysis, Glial Fibrillary Acidic Protein immunology, Inositol 1,4,5-Trisphosphate analysis, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate Receptors, Kinetics, Mice, Norepinephrine pharmacology, Rats, Receptors, Cytoplasmic and Nuclear drug effects, Receptors, Cytoplasmic and Nuclear immunology, Sympathomimetics pharmacology, Astrocytes chemistry, Astrocytes metabolism, Calcium metabolism, Calcium Channels analysis, Receptors, Cytoplasmic and Nuclear analysis
- Abstract
We have examined the mechanisms that underlie Ca2+ wave propagation in cultured cortical astrocytes. Norepinephrine evoked Ca2+ waves in astrocytes that began at discrete initiation loci and propagated throughout the cell by regenerative amplification at a number of cellular sites, as shown by very high Ca2+ release rates at these regions. We have hypothesized previously that domains displaying elevated Ca2+ release kinetics in astrocytes may correspond to sites of high inositol 1,4,5-trisphosphate receptor (InsP3R) density. To examine this possibility, we compared the distribution pattern of endoplasmic reticulum (ER) and InsP3Rs with Ca2+ release kinetics in subcellular regions during propagation of norepinephrine-evoked waves. 3,3'-Dihexyloxacarbocyanine iodide staining revealed that the ER in astrocytes exists as a meshwork of membranes extending throughout the cells, including fine processes. A specific antibody directed against type 2 InsP3Rs (InsP3R2) detected a 260-kDa band in western blotting of astrocyte membranes. Immunocytochemistry using this antibody stained the entire ER system in a punctate, variegated manner. When Ca2+ responses and InsP3R2 immunofluorescence were compared in the same cell, domains of elevated Ca2+ response kinetics (high amplitude and rapid rate of rise) showed significant positive correlation with high local intensity of InsP3R2 staining. It appears, therefore, that specializations in the ER responsible for discrete local Ca2+ release sites that support regenerative wave propagation include increased levels of InsP3R2 expression.
- Published
- 1997
- Full Text
- View/download PDF
9. Induction of tolerance in experimental autoimmune myasthenia gravis with solubilized MHC class II:acetylcholine receptor peptide complexes.
- Author
-
Spack EG, McCutcheon M, Corbelletta N, Nag B, Passmore D, and Sharma SD
- Subjects
- Amino Acid Sequence, Animals, Cell Division, Cell Line, Disease Models, Animal, Inositol 1,4,5-Trisphosphate immunology, Male, Molecular Sequence Data, Rats, Rats, Inbred Lew, T-Lymphocytes cytology, Histocompatibility Antigens Class II immunology, Immune Tolerance immunology, Myasthenia Gravis immunology, Receptors, Cholinergic immunology, T-Lymphocytes immunology
- Abstract
Stimulation of T lymphocytes through the T cell receptor in the absence of costimulatory signal(s) induces a state of unresponsiveness to subsequent antigen presentation. We have employed solubilized complexes consisting of rat class II MHC molecules containing an immunodominant peptide of the acetylcholine receptor (AChR alpha 100-116) to induce unresponsiveness in the autoreactive T lymphocytes mediating an animal model of myasthenia gravis. In vitro incubation of rat T cell lines specific for peptide AChR alpha 100-116 with solubilized complexes of MHC II and AChR alpha 100-116 (MHC II:AChR alpha 100-116) rendered the T cells unresponsive to subsequent stimulation by antigen presenting cells and the peptide. T cell lines with a broader specificity to the entire AChR protein pentamer had an 81% reduction in proliferation to AChR following a preincubation with solubilized MHC II:AChR alpha 100-116. Treatment with the solubilized MHC II:AChR alpha 100-116 induced phosphatidylinositol 4,5-bisphosphate hydrolysis, an early signalling event associated with binding to the TCR. Rats primed with AChR and injected intravenously with MHC II:AChR alpha 100-116 had reduced in vitro T cell proliferation to the AChR alpha 100-116 peptide and to whole AChR. Solubilized MHC II:AChR alpha 100-116 injected i.v. into rats exhibiting serological clinical symptoms of experimental autoimmune myasthenia gravis (EAMG) prevented death in 67% of the treated animals, compared to a 0-20% survival rate in all other control groups. These results demonstrate that solubilized MHC II complexed with an immunodominant autoantigenic peptide is tolerogenic and improves the survival rate of rats with EAMG, suggesting the basis for an antigen-specific therapy in autoimmune diseases such as MG.
- Published
- 1995
- Full Text
- View/download PDF
10. Preparation and characterization of a D-myo-inositol 1,4,5-trisphosphate-specific antibody.
- Author
-
Shieh WR and Chen CS
- Subjects
- Animals, Antibodies isolation & purification, Antibody Formation, Antibody Specificity, Antigen-Antibody Reactions, Antigens chemistry, Antigens immunology, Antigens pharmacology, Enzyme-Linked Immunosorbent Assay, Haptens chemistry, Immunoconjugates chemistry, Immunoconjugates pharmacology, Inositol 1,4,5-Trisphosphate analogs & derivatives, Inositol 1,4,5-Trisphosphate immunology, Inositol 1,4,5-Trisphosphate pharmacology, Organothiophosphorus Compounds pharmacology, Rabbits, Serum Albumin, Bovine chemistry, Serum Albumin, Bovine pharmacology, Antibodies immunology, Organothiophosphorus Compounds immunology
- Abstract
Antibodies against Ins(1,4,5)P3 were raised by immunizing rabbits with two types of InsP3-BSA conjugates which were synthesized by covalently coupling Ins(1,4,5)P3 to the carrier protein via alkyl linkages. The anti-Ins(1,4,5)P3 antibody was detected by a novel ELISA using Ins(1,4,5)P3-immobilized microtitre plates. Both antiserum preparations showed specific binding with Ins(1,4,5)P3, with titres of 1:4000. Most inositol phosphates, including Ins1P, Ins(4,5)P2, Ins(1,3,4)P3, Ins(1,5,6)P3, Ins(1,2,5,6)P1, Ins(3,4,5,6)P4, Ins(1,3,4,5,6)P5, InsP6, and PtdIns(4,5)P2, did not exhibit significant molecular interactions with the antibodies. Ins(1,3,4,5)P4, however, cross-reacted with these antibodies with one-third of the affinity as that of Ins(1,4,5)P3, in part due to the largely shared structural motifs. The differential affinity was significantly improved by affinity purification on Ins(1,4,5)P3-agarose. The affinity-purified antibody displayed IC50 values of 12 nM and 730 nM for Ins(1,4,5)P3 and Ins(1,3,4,5)P4 respectively, according to a competitive ELISA; these values are in line with those reported for the Ins(1,4,5)P3 receptor. The modes of ligand recognition at the binding sites of these two types of biomolecules are, however, different. Moreover, although the ligand binding was interfered with by multivalent anions such as ATP4-, HPO4(3-) and SO4(2-) at high concentrations, no inhibition was noted with heparin, an antagonist of the Ins(1,4,5)P3 receptor.
- Published
- 1995
- Full Text
- View/download PDF
11. Involvement of inositol 1,4,5-trisphosphate-mediated Ca2+ release in early and late events of mouse egg activation.
- Author
-
Xu Z, Kopf GS, and Schultz RM
- Subjects
- Animals, Antibodies, Monoclonal, Electrophoresis, Gel, Two-Dimensional, Female, Inositol 1,4,5-Trisphosphate immunology, Male, Maturation-Promoting Factor metabolism, Mice, Mice, Inbred Strains, Microinjections, Calcium metabolism, Inositol 1,4,5-Trisphosphate metabolism, Sperm-Ovum Interactions physiology, Zona Pellucida metabolism
- Abstract
Sperm-induced activation of mammalian eggs is associated with a transient increase in the concentration of intracellular Ca2+. The role of inositol 1,4,5-trisphosphate (IP3)-mediated release of Ca2+ from intracellular stores during mouse egg activation was examined in the present study by determining the effects of microinjected monoclonal antibody (mAb) 18A10, which binds to the IP3 receptor and inhibits IP3-induced Ca2+ release, on endpoints of egg activation following insemination. The antibody inhibited in a concentration-dependent manner the ZP2 to ZP2f conversion that is involved in the zona pellucida block to polyspermy, as well as the ZP2 to ZP2f conversion promoted by microinjected IP3 in non-inseminated eggs. As anticipated, inseminated eggs that had been microinjected with the antibody were polyspermic. In addition, the antibody inhibited the fertilization-associated decrease in H1 kinase activity and pronucleus formation, and the concentration dependence for inhibition of these events was similar to that observed for inhibiting the ZP2 to ZP2f conversion. Last, the antibody inhibited the fertilization-induced recruitment of maternal mRNAs and post-translational modifications of proteins. In each case, eggs microinjected with the mAb 4C11, which also binds to the IP3 receptor but does not inhibit IP3-induced Ca2+ release, had no inhibitory effect on fertilization and egg activation. Results of these studies suggest that IP3-mediated Ca2+ release is essential for both early and late events of mouse egg activation.
- Published
- 1994
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.