Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have sought to elucidate the responses of human peripheral blood neutrophils to antigenic surfaces complexed with human specific IgA antibodies obtained either as myeloma proteins that recognize staphylococcal alpha-toxin, or from the serum of patients with subacute bacterial endocarditis due to Streptococcus mutans, or from colostrum. In contrast to IgG, IgA antibodies bound to antigen-coated fluorescent microspheres, and subsequently exposed to complement (or not), did not promote phagocytosis, as measured by flow cytometric enumeration of cell-associated microspheres. Instead, IgA antibodies interfered with complement-dependent phagocytosis mediated by IgG antibodies. These properties were shown by different forms of IgA antibodies, including serum and secretory IgA, as well as by monoclonal or polyclonal antibodies. Neutrophils did not respond to the production of superoxide to IgA antibodies complexed with antigen-coated microspheres or with antigen deposited on a solid surface and IgA antibodies suppressed IgG antibody- and complement-mediated superoxide release. However, neutrophils pretreated with interleukin-8 ingested IgA-opsonized microspheres and released superoxide when exposed to IgA antibody-antigen complexes. IgG antibody-antigen complexes did not stimulate increased superoxide release in interleukin-8-treated neutrophils. These findings were consistent with a selective increase in the surface expression of Fc alpha R by interleukin-8-treated neutrophils. We conclude that IgA antibodies interfere with the phagocytic activities of normal circulating human neutrophils and may promote these activities in inflammatory neutrophils activated by interleukin-8 in which Fc alpha R is up-regulated.
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PMID:Dual function of human IgA antibodies: inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells. 779 Jul 70

It is envisaged that circulating IgA complexes play a primary role in the glomerular injury of IgA nephropathy, the most common glomerulonephritis worldwide. In this study, we examined the pathophysiological effects of IgA and IgG isolated from IgA-nephritic patients on the signal transduction of human neutrophils. Heat-aggregated forms and monomers of IgA and IgG were prepared from sera of 11 IgA-nephritic patients and 11 healthy controls. Signal transduction was studied by measuring the inositol triphosphate (IP3) production in neutrophils incubated with the immunoglobulin preparations. Different forms of IgA or IgG from IgA-nephritic patients failed to induce a significant increase in IP3 production directly as compared with control IgA or IgG. However, neutrophils preincubated with heat-aggregated IgA (HAA) from IgA-nephritic patients demonstrated a significant rise in IP3 production upon subsequent stimulation by a chemotactic peptide, FMet-Leu-Phe (FMLP); a similar finding was not observed with heat-aggregated IgG. HAA pretreatment of neutrophils increased FMLP-induced IP3 production in a dose-dependent manner. The raised IP3 production was not due to increased FMLP receptors, as HAA preincubation of neutrophils did not increase the binding of tritiated FMLP. The increased IP3 production upon FMLP stimulation in HAA-primed neutrophils was completely abolished by pertussis toxin in a dose-dependent manner. These findings tend to refute a direct stimulatory effect of HAA on phospholipase C, but, instead, may suggest that HAA prepared from IgA-nephritic patients upregulates the activation of G proteins in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heat-aggregated IgA prepared from patients with IgA nephropathy increases priming of human neutrophils to produce inositol triphosphate following FMet-Leu-Phe stimulation in vitro. 789 78

Concanavalin A (Con A)-binding glycoproteins accelerate the rate of cholesterol crystal formation as a prelude to gallstone formation. Immunoglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha 1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of the six putative promoters and examined their comparative effects by adding equal amounts to a cholesterol crystal growth assay. The effects of immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the potency of these proteins was in the following order: IgM > IgA = AAG > IgG. APN and pcPLC showed no effect on cholesterol crystal growth at their apparent physiological concentrations. In subtractive experiments, only a minor loss (< 10%) of net promoting activity from that of the whole Con A-bound fraction was observed after immunoabsorptive removal of pcPLC, APN, or immunoglobulins. Total removal of AAG, however, showed a far greater loss (/33%) of the net promoting activity. These data indicate that AAG accounts for the greatest portion of net biliary Con A-bound promoting activity derived from currently defined and well-identified glycoproteins. However, more than 60% of total Con A-binding promoting activity remains unaccounted for, indicating the presence of other important and still unidentified promoters in human bile.
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PMID:Cholesterol crystallization-promoters in human bile: comparative potencies of immunoglobulins, alpha 1-acid glycoprotein, phospholipase C, and aminopeptidase N1. 810 87

Polyclonal human secretory IgA1 and IgA2 antibodies to a bacterial protein antigen Streptococcus mutans AgI/II, and polyclonal human serum IgA1 and IgA2 antibodies to staphylococcal alpha-toxin, were found to interfere with antigen-mediated C3b fixation. In fluid phase, immune complexes of antigen and IgA failed to fix C3b, whereas antigen-IgG complexes did fix C3b. Partial removal of glycan chains with Streptococcus mitis SK96 glycosidases diminished the capacity of IgA antibodies to interfere with antigen-mediated C3b fixation by the alternative complement pathway. The authors conclude that native serum or secretory IgA antibodies suppress C3b fixation, and that the glycan chains play a significant role in maintaining this property.
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PMID:All forms of human IgA antibodies bound to antigen interfere with complement (C3) fixation induced by IgG or by antigen alone. 812 87

Although knowledge of IgA Fc receptor (Fc(alpha)R) structure and gene organization has progressed in the past few years, signal transduction pathways elicited by its activation have hardly been studied. Previously, we have demonstrated that mesangial cells (MC) possess Fc(alpha)R stimulation triggers several biologic responses. In this work, we studied the early biochemical signals triggered by Fc(alpha)R stimulation in MC. MC incubation with aggregated IgA (AIgA) elicited a dose-dependent increase in cytosolic Ca2+ ([Ca2+]i). The response was rapid and transient, and slowly fell to the original baseline. Ca2+ mobilization was dependent on the Fc region of the IgA, because Fc, but neither Fab fragment nor carbohydrates, inhibited the [Ca2+] rise. The initial induction of [Ca2+]i rise was due to Ca2+ mobilization from inositol trisphosphate (IP3)-sensitive intracellular stores, while sustained levels were maintained through extracellular Ca2+ influx. Stimulation of Fc(alpha)R also resulted in production of IP3, temporally correlated with Ca2+ mobilization. Protein tyrosine kinase inhibitors abolished [Ca2+]i rise, indicating that tyrosine phosphorylation of some substrates is required for Ca2+ mobilization. Stimulation through Fc(alpha)R gave rise to a marked increase in tyrosine phosphorylation of several proteins, including the 147-kDa band, similar in size to phospholipase C-gamma(1) (PLC-gamma(1)). Tyrosine phosphorylation of PLC-gamma(1) reached a maximum 30 s after stimulation, as determined by immunoprecipitation and Western blot. Collectively, these results indicate that the Fc(alpha)R signaling pathway in MC involves PLC-(gamma(1) activation, IP3 formation, and Ca2+ mobilization, and is linked to activation of tyrosine kinases.
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PMID:Stimulation of Fc(alpha) receptors induces tyrosine phosphorylation of phospholipase C-gamma(1), phosphatidylinositol phosphate hydrolysis, and Ca2+ mobilization in rat and human mesangial cells. 866 9

One of the hallmarks of mucosal-host defense is the clearance of inhaled Ags by alveolar macrophages (AM) through interactions of IgA Abs and IgA Fc receptors (Fc alpha R). AM constitutively expressed Fc alpha R at lower levels than freshly isolated and in vitro-differentiated monocytes as determined by immunofluorescence using four anti-Fc alpha R mAb. SDS-PAGE analysis of iodinated cell surface proteins revealed that Fc alpha R on AM has an Mr of 50 to 65 kDa, slightly lower than that on monocytes (55-75 kDa). Treatment of AM Fc alpha R by N-glycanase gave rise to a protein core of 28 KDa, smaller than the 32-kDa backbone of blood monocytes. AM Fc alpha R molecules were unaffected by phosphatidylinositol-phospholipase C treatment. Fc alpha R transcripts were analyzed by reverse transcription-PCR using primers in the 5' and 3' regions of a U937 Fc alpha R cDNA. Three transcripts were amplified, cloned, and sequenced from AM and/or monocyte mRNA, the full length Fc alpha R and two alternatively spliced products corresponding to deletions of 66 and 288 nucleotides in the portion coding for the extracellular domain; they were named Fc alpha R a.1, a.2, and a.3, respectively. These PCR products were transcribed and translated in vitro into three proteins (Mr 32, 30, and 22 kDa, respectively), in which the 32- and 30-kDa species were immunoprecipitated by an anti-Fc alpha R mAb. The predicted size of the protein encoded by the Fc alpha R a.2 transcript without the leader peptide is Mr approximately 27,400, a value that is consistent with the Mr of AM Fc alpha R backbone. These results indicate that AM express at their surfaces a protein product of an alternatively spliced Fc alpha R transcript, the Fc alpha R a.2 isoform, that might have physiologic relevance in IgA-mediated host defense at mucosal sites.
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PMID:Identification of Fc alpha receptor (CD89) isoforms generated by alternative splicing that are differentially expressed between blood monocytes and alveolar macrophages. 866 19

The Fc receptor for IgA (Fc alpha R, CD89) is a transmembrane glycoprotein found on monocytes, macrophages, neutrophils, and eosinophils. Here we describe the characterization of a novel isoform of the Fc alpha R cloned from a human eosinophil cDNA library. This clone, Fc alpha Rb, lacks the exon encoding the transmembrane/intracellular region of wild type Fc alpha R, which is replaced by 23 new amino acids. Expression of Fc alpha Rb mRNA could be detected in eosinophils and neutrophils. IIA1.6 murine pro-B cells transfected with Fc alpha Rb cDNA secrete high levels of the protein, but also a substantial amount of Fc alpha Rb is expressed at the cell membrane. Membrane-bound Fc alpha Rb binds IgA-coated beads equally well as wild type Fc alpha R. Surface expression is not affected by phosphatidyl inositol phospholipase C, indicating that glycosyl phosphatidyl inositol-linkage of Fc alpha Rb is not likely. In IIA1.6 cells expressing Fc alpha Rb and FcR gamma, which is necessary for signal transduction by wild type Fc alpha R, no tyrosine phosphorylation or Ca(2+)-mobilization could be observed after receptor cross-linking. These results indicate that Fc alpha Rb is likely to have a different function than wild-type Fc alpha R receptor.
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PMID:Cloning and characterization of Fc alpha Rb, a novel Fc alpha receptor (CD89) isoform expressed in eosinophils and neutrophils. 894 58

The Immunoglobulin (Ig) binding capacity of Toxoplasma gondii tachyzoites was investigated using fluorescence flow-cytometry analysis. Polyclonal mouse, human and rat immunoglobulins without specific anti-Toxoplasma activity bound to parasites in a concentration-dependent manner, saturating them at circulating serum concentrations. The immunoglobulin class and subclass specificity of binding was investigated using irrelevant monoclonal antibodies. IgM, IgA and IgG reacted with the parasite membrane. The attachment of mouse IgM to the parasite surface was hampered by mouse IgG1, IgG2a, IgG2b and IgG3. The binding of mouse IgG was proportionally reduced with increasing concentrations of mouse monoclonal IgM. The binding of murine immunoglobulin was diminished when in presence of human IgG. Purified Fc- but not Fab portions of immunoglobulins, fixed to parasites. Using labelled calibrated beads, the Ig binding capacity of parasites was estimated to be 6900 +/- 500 sites per tachyzoite. The Kd of the T. gondii Fc Receptor (FcR) activity was determined at 1.4 +/- 0.1 microM (mean +/- SEM). Such FcR activity was reduced by phospholipase C, trypsin and pronase treatment of the parasites. These data show a low affinity FcR activity on T. gondii tachyzoites which recognizes Ig of different species and isotypes and is likely supported by a glycosyl-phosphatidylinositol (GPI)-anchored surface protein of the parasite.
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PMID:Identification and characterization of a Fc receptor activity on the Toxoplasma gondii tachyzoite. 949 16

The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA), from the basolateral to the apical surface of epithelial cells. Although the pIgR is constitutively transcytosed in the absence of ligand, binding of dIgA stimulates transcytosis of the pIgR. We recently reported that dIgA binding to the pIgR induces translocation of protein kinase C, production of inositol triphosphate, and elevation of intracellular free calcium. We now report that dIgA binding causes rapid, transient tyrosine phosphorylation of several proteins, including phosphatidyl inositol-specific phospholipase C-gammal. Protein tyrosine kinase inhibitors or deletion of the last 30 amino acids of pIgR cytoplasmic tail prevents IgA-stimulated protein tyrosine kinase activation, tyrosine phosphorylation of phospholipase C-gammal, production of inositol triphosphate, and the stimulation of transcytosis by dIgA. Analysis of pIgR deletion mutants reveals that the same discrete portion of the cytoplasmic domain, residues 727-736 (but not the Tyr734), controls both the ability of pIgR to cause dIgA-induced tyrosine phosphorylation of the phospholipase C-gammal and to undergo dIgA-stimulated transcytosis. In addition, dIgA transcytosis can be strongly stimulated by mimicking phospholipase C-gammal activation. In combination with our previous results, we conclude that the protein tyrosine kinase(s) and phospholipase C-gammal that are activated upon dIgA binding to the pIgR control dIgA-stimulated pIgR transcytosis.
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PMID:Role of tyrosine phosphorylation in ligand-induced regulation of transcytosis of the polymeric Ig receptor. 965 71

The role of the Wiskott-Aldrich syndrome protein (WASp) in platelet function is unclear because platelets that lack WASp function normally. WASp constitutively associates with WASp-interacting protein (WIP) in resting and activated platelets. The role of WIP in platelet function was investigated using mice that lack WIP or WASp. WIP knockout (KO) platelets lack WASp and thus are double deficient. WIP KO mice have a thrombocytopenia, similar to WASp KO mice, resulting in part from enhanced platelet clearance. Most WIP KO, but not WASp KO, mice evolved platelet-associated immunoglobulins (Ig) of the IgA class, which normalize their platelet survival but diminish their glycoprotein VI (GPVI) responses. Protein tyrosine phosphorylation, including that of phospholipase C-gamma2, and calcium mobilization are impaired in IgA-presenting WIP KO platelets stimulated through GPVI, resulting in defects in alpha-granule secretion, integrin alphaIIbbeta3 activation, and actin assembly. The anti-GPVI antibody JAQ1 induces the irreversible loss of GPVI from circulating platelets in wild-type mice, but not in WIP KO mice that bear high levels of platelet-associated IgAs. Together, the data indicate that platelet-associated IgAs negatively modulate GPVI signaling and function in WIP KO mice.
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PMID:Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP. 1996 14


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