Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antigenic and allergenic properties of phospholipase A2 (PLA2) and whole bee venom were compared by measuring the IgG and IgE antibody responses in animals and man. Precipitating antibodies raised in rabbits and reaginic and other antibodies raised in mice reacted about equally with both bee venom and PLA. The majority of human sera containing bee venom-specific IgE also contained PLA-specific IgE, although in somewhat lower titers. Similarly, most human sera with significant amounts of total antibodies reacting with bee venom also had antibodies reacting with PLA. Histamine and SRS-a release from leukocytes of sensitive patients followed challenge with whole bee venom and PLA in the majority of instances. However, mediator release from several patients' cells was obtained with bee venom only. These studies suggest that although PLA is a major allergen and antigen in bee venom, significant exceptions in patients' reactivity may limit its potential diagnostic and therapeutic usefulness.
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PMID:Studies of the antigenicity and allergenicity of phospholipase A2 of bee venom. 5 45

Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases).
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PMID:Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes. 608 35

REV 3164 has been evaluated in a variety of intact rodent models to reveal potential utility in the prophylactic treatment of asthma. REV 3164 was found a potent, orally active inhibitor of rat (IgE) passive cutaneous anaphylaxis (PCA, ED50 = 0.9 mg/kg). By contrast, at 50-200 mg/kg p.o., it did not affect guinea-pig (IgG1) PCA. In PCA rats, both REV 3164, 1-36 mg/kg i.p., and the known inhibitor of mast cell mediator release, disodium cromoglycate (DSCG), 2-54 mg/kg i.p., blocked cutaneous wheals caused by i.v. antigen challenge but not by intradermal serotonin or histamine. Neither REV 3164 (0.1-10 mg/kg i.p.) nor DSCG (2-54 mg/kg i.p.) affected Compound 48/80-induced wheals. REV 3164 (0.01-1 mg/kg i.v. or 10 mg/kg i.p.) abolished rat (IgE) passive lung anaphylaxis (PLA, ED50 = 0.05 mg/kg i.v. for inhibition of elevated airway resistance). At 10 mg/kg i.p., REV 3164 did not affect active lung anaphylaxis in guinea-pigs pharmacologically manipulated to enhance the production and action of slow reacting substance of anaphylaxis (SRS-A), nor did it exhibit anticholinergic activity in the rat. REV 3164 (100 mg/kg i.p.) did not protect conscious guinea-pigs from histamine aerosol-induced collapse. It is concluded that REV 3164 is an oral inhibitor of IgE-dependent immediate hypersensitivity in the rat with biological activities in rats and guinea-pigs similar to DSCG.
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PMID:In vivo anti-allergic and bronchopulmonary pharmacology of REV 3164 in rats and guinea-pigs. 649 6

Alveolar macrophage (AMO) were recovered by bronchoalveolar lavage from mice. We have examined the surface of these cells for receptors of immune effector molecules and compared the normal resident AMO to the 'activated' cell present during extensive lung inflammation caused by the parasite Nippostrongylus brasiliensis 2 days after subcutaneous inoculation. As has been shown previously, the resident alveolar macrophage expresses Fc receptors for IgG (90%) and IgE (17%). We now show that a significant proportion of resident AMO possess an Fc receptor for IgA (14%) and this proportion increases to nearly 30% upon activation of the cell, coincident with an increase in release of plasminogen activator and phagocytic activity. This newly described presence of IgA receptors on AMO represents an important demonstration of potential 'arming' of these cells by the predominant antibody in mucous secretions and direct involvement of the AMO in immune mediated reactions in the lung.
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PMID:Fc receptors for IgA and other immunoglobulins on resident and activated alveolar macrophages. 668 17

Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag-coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy.
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PMID:Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice. 1120 23

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by FcepsilonRI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A(1), PS-PLA(1), stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of FcepsilonRI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA(1), in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA(1) significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin, which has affinity for PS-PLA(1), completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.
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PMID:Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine. 1139 20

Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum are the important characteristic features of asthma. We evaluated the potential of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as assessed by airway constriction and airway hyperreactivity (AHR) to methacholine (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect on airway constriction and AHR to MCh. Determination of OVA-induced airway constriction and AHR to MCh were performed by measuring specific airway conductance (SGaw) using non-invasive dual-chamber whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN-gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5 (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of modulating allergen induced cytokine levels and serum IgE levels, and alleviating allergen induced airway hyperresponsiveness and eosinophils in mice. These data suggest that PBPB could be useful in the development of novel agents for the treatment of allergen induced airway hyperresponsiveness.
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PMID:Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice. 1545 21

Activation of mouse bone marrow-derived mast cells (BMMC) with stem cell factor (SCF) or IgE and antigen elicits exocytosis and an immediate phase of prostaglandin (PG) D(2) and leukotriene (LT) C(4) generation. Activation of BMMC by SCF, IL-1beta and IL-10 elicits a delayed phase of PGD(2) generation dependent on cyclooxygenase (COX) 2 induction. Cytosolic phospholipase A(2) alpha provides arachidonic acid in both phases and amplifies COX-2 induction. Pharmacological experiments implicate an amplifying role for secretory (s) PLA(2). We used mice lacking the gene encoding group V sPLA(2) (Pla2g5-/-) to definitively test its role in eicosanoid generation by BMMC. Pla2g5-/- BMMC on a C57BL/6 genetic background showed a modest reduction in exocytosis and immediate PGD(2) generation after activation with SCF or with IgE and antigen, while LTC(4) generation was not modified. Delayed-phase PGD(2) generation and COX-2 induction were reduced approximately 35% in C57BL/6 Pla2g5-/- BMMC and were restored by exogenous PGE(2). There was no deficit in either phase of eicosanoid generation by Pla2g5-/- BMMC on a BALB/c background. Thus, group V sPLA(2) amplifies COX-2 expression and delayed phase PGD(2) generation in a strain-dependent manner; it has at best a limited role in immediate eicosanoid generation by BMMC.
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PMID:Group V secretory phospholipase A2 amplifies the induction of cyclooxygenase 2 and delayed prostaglandin D2 generation in mouse bone marrow culture-derived mast cells in a strain-dependent manner. 1706 58

The biochemical and functional characterization of wasp venom toxins is an important prerequisite for the development of new tools both for the therapy of the toxic reactions due to envenomation caused by multiple stinging accidents and also for the diagnosis and therapy of allergic reactions caused by this type of venom. PLA(1) was purified from the venom of the neotropical social wasp Polybia paulista by using molecular exclusion and cation exchange chromatographies; its amino acid sequence was determined by using automated Edman degradation and compared to the sequences of other vespid venom PLA(1)'s. The enzyme exists as a 33,961.40 Da protein, which was identified as a lipase of the GX class, liprotein lipase superfamily, pancreatic lipases (ab20.3) homologous family and RP2 sub-group of phospholipase. P. paulista PLA(1) is 53-82% identical to the phospholipases from wasp species from Northern Hemisphere. The use restrained-based modeling permitted to describe the 3-D structure of the enzyme, revealing that its molecule presents 23% alpha-helix, 28% beta-sheet and 49% coil. The protein structure has the alpha/beta fold common to many lipases; the core consists of a tightly packed beta-sheet constituted of six-stranded parallel and one anti-parallel beta-strand, surrounded by four alpha-helices. P. paulista PLA(1) exhibits direct hemolytic action against washed red blood cells with activity similar to the Cobra cardiotoxin from Naja naja atra. In addition to this, PLA(1) was immunoreactive to specific IgE from the sera of P. paulista-sensitive patients.
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PMID:Purification, sequencing and structural characterization of the phospholipase A1 from the venom of the social wasp Polybia paulista (Hymenoptera, Vespidae). 1776 Dec 5

Asthma is a dynamic disorder of airway inflammation and airway remodeling with an imbalance in T helper type 1 (Th(1))/Th(2) immune response. Increased Th(2) cytokines such as IL-4 and IL-13 induce arginase either directly or indirectly through transforming growth factor-beta(1) (TGF-beta(1)) and lead to subepithelial fibrosis, which is a crucial component of airway remodeling. Synthetic antimalarials have been reported to have immunomodulatory properties. Mepacrine is known for its reduction of airway inflammation in short-term allergen challenge model by reducing Th(2) cytokines and cysteinyl leukotrienes, which has an important role in the development of airway remodeling features. Therefore, we hypothesized that mepacrine may reduce airway remodeling. For this, extended subacute ovalbumin mice model of asthma was developed; these mice showed an increased expression of profibrotic mediators, subepithelial fibrosis, and goblet cell metaplasia along with airway inflammation, increased Th(2) cytokines, allergen-specific IgE, IgG(1), increased cytosolic PLA(2) (cPLA(2)), and airway hyperresponsiveness. Presence of intraepithelial eosinophils and significant TGF-beta(1) expression in subepithelial mesenchymal regions by repeated allergen exposures indicate that asthmatic mice of this study have developed human mimicking as well as late stages of asthma. However, mepacrine treatment decreased Th(2) cytokines and subepithelial fibrosis and alleviated asthma features. These reductions by mepacrine were associated with a decrease in levels and expression of TGF-beta(1) and the reduction in activity, expression of arginase in lung cytosol, and immunolocalization in inflammatory cells present in perivascular and peribronchial regions. These results suggest that mepacrine might reduce the development of subepithelial fibrosis by reducing the arginase and TGF-beta(1). These effects of mepacrine likely underlie its antiairway remodeling action in asthma.
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PMID:Mepacrine inhibits subepithelial fibrosis by reducing the expression of arginase and TGF-beta1 in an extended subacute mouse model of allergic asthma. 1954 46


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