PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “STING Protein”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes.

Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI cross-linking in sensitized individuals.

Allergens↗
PubMed2004

Negative effect of antibodies against maxadilan on the fitness of the sand fly vector of American visceral leishmaniasis.

Lutzomyia longipalpis expresses a salivary protein called maxadilan (MAX) that functions to dilate vertebrate blood vessels and thereby to facilitate the sand fly's acquisition of blood. We hypothesized that antibodies specific for one of many MAX variants would inhibit vasodilatory function of that variant. In vitro and in vivo experiments showed that antibodies against a specific MAX variant decreased vasodilatory function. More specifically, antibodies against MAX blocked vasodilation of a constricted rabbit aorta. Additionally, a strain of Lu. longipalpis, with a nearly uniform MAX genotype, obtained a larger blood meal from naive BALB/c mice compared with mice that were either immunized with a homologous MAX genotype or sensitized to bites of flies from the same strain. Those flies taking blood from mice sensitized by sand fly bites also laid significantly fewer eggs than when they took blood from naive mice. These results have potential epidemiologic importance in light of the potential use of MAX in a vaccine or as part of a diagnostic test because they imply that a uniform MAX genotype is selected against by the vertebrate host immune response and that antigenic diversity is selected for.

Animals↗
PubMed1999

Induction of IgE responses using a recombinant mosquito salivary allergen rAed a 2 without adjuvant in mice.

BACKGROUND: Reactions to mosquito bites are a global problem. Several salivary proteins from Aedes (Ae.) aegypti, the most common mosquito species, have been cloned and expressed. Plasmid DNA vaccination has been shown to be effective in the downregulation of IgE responses. To investigate the in vivo antigenicity of these recombinant proteins and to study the mechanisms underlying plasmid DNA vaccination, a mouse model sensitized with a recombinant antigen has been developed. METHODS: BALB/c and C57BL/6 mice were injected intradermally with a 37-kD recombinant Ae. aegypti salivary allergen (rAed a 2) in the absence of adjuvant twice weekly for 8 weeks and then challenged twice with rAed a 2 at weeks 10 and 12. Serum rAed a 2-specific IgE, IgG1 and IgG2a were measured by ELISA. Intradermal tests were performed every 4 weeks. The binding capacity of rAed a 2-specific IgE to the native Aed a 2 was examined by immunoblotting. RESULTS: In both strains, sensitization with rAed a 2 induced a significant increase in IgE and IgG1, but not IgG2a. In all sensitized mice, a positive immediate skin reaction was apparent, while delayed-type hypersensitivity reactions were not observed. BALB/c mice produced significantly higher levels of IgE and IgG1 and larger wheals than C57BL/6 mice. The IgE antibodies elicited by rAed a 2 bound to not only rAed a 2 but also its natural form in mosquito saliva. CONCLUSION: (1) Repeated injections of rAed a 2 without adjuvant induce predominant Th2-type responses in mice. (2) BALB/c mice are better responders for IgE production than C57BL/6 mice. (3) rAed a 2 has identical allergenicity to its natural form.

Adjuvants, Immunologic↗
PubMed2006

A new recombinant mosquito salivary allergen, rAed a 2: allergenicity, clinical relevance, and cross-reactivity.

BACKGROUND: Mosquito salivary proteins cause allergic reactions in humans. The allergenicity, clinical relevance, and species cross-reactivity of a new 37-kDa recombinant mosquito (Aedes aegypti) salivary allergen, rAed a 2, were evaluated. METHODS: rAed a 2 was expressed using a baculovirus/insect cell system and purified. Its allergenicity was examined using an enzyme-linked immunosorbent assay (ELISA), ELISA inhibition tests, immunoblots, and skin tests. Epicutaneous tests with the allergen, mosquito whole body extracts, and mosquito bite tests were performed on 48 volunteers. Serum rAed a 2-specific immunoglobulin E (IgE) was measured in individuals with positive mosquito saliva-specific IgE and negative controls. RESULTS: Both immunoblots and ELISAs demonstrated that rAed a 2 bound to the IgE of mosquito-allergic individuals. The binding could be inhibited by the addition of a natural mosquito preparation. Furthermore, rAed a 2 induced immediate and delayed skin reactions. Ten per cent of 31 participants with a positive mosquito bite test had positive skin reactions to rAed a 2, compared with 32% for mosquito whole body extract. None of the participants with a negative bite test showed positive reactions to either of the two extracts. Forty-three per cent of individuals with positive saliva-IgE had positive rAed a 2-IgE. rAed a 2 was a species-shared allergen, being present in the saliva of the 11 species studied. CONCLUSIONS: rAed a 2 has identical antigenicity and biologic activity to its native form. It can be used in the diagnosis of mosquito allergy, and is an important species-shared antigen.

Adult↗
PubMed1996

Modeling immunotherapy for allergy.

Type I hypersensitivity, which functions to protect the organism from parasites, is caused by binding of antigen to IgE antibodies pre-attached to the cell surface of tissue mast cells and their circulating counterparts, the basophils. In "allergy," type I hypersensitivity is inappropriately induced by protein-based foreign substances (such as pollen) or protein components of insect stings, which in the normal course of events would be cleared from the organism without causing any damage. Paradoxically, a successful clinical treatment of allergy involves repeated immunization of allergic persons with low doses of the allergen--immunotherapy. Investigation of the available experimental evidence leads to the conclusion that the phenomena of immunotherapy are best addressed in terms of the interplay among the mechanism(s) of immune memory--Th1/Th2 cross-regulation--and the physical compartmentalization of the immune system. These conclusions are illustrated with a numerical simulation.

Animals↗
PubMed2001

Triapsin, an unusual activatable serine protease from the saliva of the hematophagous vector of Chagas' disease Triatoma infestans (Hemiptera: Reduviidae).

Salivary anticoagulant activities are widely distributed among hematophagous arthropods. Most of them are inhibitors of the serine proteases of the coagulation cascade. Here we show that the saliva of the exclusively hematophagous insect Triatoma infestans, an important vector in the transmission of Chagas' disease, contains an uncommon trypsin-like activity, triapsin. This novel enzyme was purified and characterized. It is a serine protease that is stored as a zymogen in the luminal content of the salivary glands D2. Triapsin is activated by trypsin treatment, or when the saliva is ejected during the insect bite. The enzyme was purified 300-fold from the released saliva by anion exchange chromatography in a HiTrap Q column, followed by chromatography in Phenyl-Superose, and Superdex HR75. The purified triapsin shows an apparent molecular mass of around 40 kDa in non-reduced SDS gels and in sieving chromatography, and 33 kDa in reduced SDS-gels. Its activity is lost after incubation with dithiothreitol indicating that cysteine bridges are essential for activity. Triapsin cleaves gelatin and synthetic substrates showing preference for arginine at P1 residues. The best p-nitroanilide substrate is isoleucyl-prolyl-arginine. It does not cleave bradykinin, angiotensin and other lysine containing substrates. The triapsin amidolytic activity against chromogenic substrates is similar to plasminogen activators, such as urokinase and tissue plasminogen activator. However, it does not activate plasminogen. The fact that triapsin is released at the bite in its active form suggests that it has a role in blood feeding.

Animals↗
PubMed2001

Anaphylaxis caused by the new ant, Pachycondyla chinensis: demonstration of specific IgE and IgE-binding components.

BACKGROUND: There have been no reports dealing with the pathogenic mechanism and IgE-binding components in patients with anaphylaxis caused by a sting from Pachycondyla chinensis. OBJECTIVES: This study was conducted to observe the clinical features of patients with P chinensis -induced anaphylaxis. The roles of specific (s) IgE and sIgG4 antibodies were evaluated, and IgE-binding components were identified. METHODS: Seven patients with P chinensis -induced anaphylaxis and 15 unexposed control subjects were enrolled. P chinensis ants were collected at the patients' homes, and venom was prepared as P chinensis extract. Five patients complained of bee venom-induced anaphylaxis and had positive sIgE levels to yellow jacket venom, wasp venom, or both as well. Serum sIgE and sIgG4 were detected by means of ELISA. To identify IgE-binding components within P chinensis extracts, 12% SDS-PAGE with immunoblot analysis was applied. RESULTS: All patients had positive skin prick test responses to P chinensis antigen and positive sIgE levels. Five (71%) patients had positive sIgG4 levels. Eight IgE-binding components (58, 46, 3l, 29, 27, 25, 22, and 12 kd) were noted, and the component at 12 kd was the most frequently found allergen (85%). IgE ELISA inhibition tests were performed on 2 groups of sera: one from patients with anaphylaxis induced by both P chinensis and bee venom (group A) and the other from patients with anaphylaxis induced by P chinensis venom alone without bee venom allergy (group B). ELISA inhibition tests with serum from group A showed significant inhibitions with addition of P chinensis extract, partial inhibitions with yellow jacket antigen, and minimal inhibitions with wasp or imported fire ant antigens. However, ELISA inhibition tests with serum from group B showed significant inhibitions with P chinensis antigen but no inhibition with wasp, yellow jacket, or imported fire ant antigens. CONCLUSIONS: IgE-mediated reactions contributed to the development of P chinensis -induced anaphylaxis. Eight IgE-binding components and one major allergen (12 kd) were identified. Further studies will be needed to clarify the role of sIgG4 and to identify allergenic relationships with major bee and wasp allergens.

Adult↗
PubMedDate not supplied

Life-threatening facial edema due to pine caterpillar mimicking an allergic event.

BACKGROUND: Approximately 150 species of Lepidoptera have been described as causing damage to human skin. One of these species is the pine processionary caterpillar, which is responsible for dermatitis, contact urticaria, ocular lesions and rarely respiratory signs and anaphylactic reactions through IgE-mediated or non-IgE-mediated mechanisms. We report a pediatric case of severe orofacial edema mimicking an allergic reaction after ingestion of a pine processionary caterpillar; urgent airway intubation was required. CASE REPORT: A 15-month-old boy was sleeping under a pine tree when his mother noted a pine caterpillar on his tongue. Because of rapidly developing facial swelling and respiratory distress, the infant was first taken to a local hospital where he received intravenous dexamethasone and pheniramine hydrogen maleate. On arrival at our emergency department, diffuse swelling and edema involving the tongue, perioral, nasal and perimandibular regions, and neck was noted, requiring urgent orotracheal intubation. There were no findings of anaphylaxis. The results of skin prick tests and specific IgE to common aero- and food allergens were negative. A skin prick test with extract of pine caterpillar was also negative. Prednisolone and pheniramine hydrogen maleate were administered for 7 days. The child gradually improved and was successfully extubated 4 days later. CONCLUSION: Although oral contact with a pine processionary caterpillar in the form of ingestion is rare, it may cause significant local reaction and airway compromise mimicking an allergic event. In this situation, early intubation to maintain airway patency is a life-saving measure.

Airway Obstruction↗
PubMedDate not supplied

Mosquito allergy: recombinant mosquito salivary antigens for new diagnostic tests.

In patients with mosquito allergy, lack of a readily available, sensitive, specific, safe test is the major obstacle to accurate diagnosis. Three recombinant mosquito salivary antigens, rAed a 1 (68 kD), rAed a 2 (37 kD) and rAed a 3 (30 kD), from Aedes aegypti have been cloned, expressed, purified and characterized. All three recombinant antigens are shared by Aedes vexans and other mosquito species, and all have been found to have biologic activity in humans. In recent studies, 43% of 28 mosquito bite test-positive subjects had a positive skin test to rAed a 1, 11% to rAed a 2 and 32% to rAed a 3. The sizes of the skin test reactions to the recombinant antigens correlated with the sizes of the A. aegypti bite test reactions. None of 15 A. aegypti bite test-negative subjects had a positive skin test to any of the recombinant antigens. Recombinant mosquito salivary antigens will facilitate the diagnosis of mosquito allergy.

Aedes↗
PubMed2004

Mosquito allergy: immune mechanisms and recombinant salivary allergens.

Reactions to mosquito bites are immunological in nature, with the involvement of IgE-, IgG- and T lymphocyte-mediated hypersensitivities. Acquired desensitization to mosquito saliva may occur during childhood and adolescence or during long-term exposure to mosquito bites. Due to the lack of salivary preparations, allergic reactions to mosquito bites are underdiagnosed and undertreated. Recombinant mosquito saliva allergens with biological activity are being developed. These recombinant allergens will significantly improve diagnosis of mosquito allergy and eventually will also improve specific immunotherapy for patients with systemic reactions to mosquito bites.

Adolescent↗
PubMed2002

[Theoretical and experimental bases for treatment of scorpion envenomations].

Improving the efficacy of envenomation treatment depends on what is known about active molecules present in venoms. Regarding scorpions, studies carried out mainly on the most poisonous species have shown that the toxicity and mortality were due to small proteins-toxins--able to interfere with the normal process of the ionic channels. In certain cases, using the mouse model, it has been shown that over 90% of mortality was due to toxins operating on the sodium channels implicated in the action potential of the excitable cells. Pharmacokinetic studies have shown the diversity of their mode of action implying an adaptation of the means and tools intended to neutralise them. The toxins active on the sodium channels represent a family of proteins from 60 to 65 amino acids linked by 4 disulphide bridges with a very strong antigenic polymorphism; this has certain implications in terms of paraspecificity of antivenoms. The problem is even more complicated when one considers the variation of toxin quantity from one animal to another of the same species. Another approach is to identify the most active and represented toxins in venoms for each antigenic group and to develop a means of neutralizing them. It would also be possible to define toxoids for use either in the production of the antivenoms or as immunological protection for individuals at risk. Lastly, where symptomatic treatment is concerned, certain drugs such as aspirin, quinine or dandrolene have been shown definitely to increase the value of the LD50 in the mouse.

Action Potentials↗
PubMedDate not supplied

[Itching caused by insects].

Papular urticaria is a cutaneous manifestation caused by the sensitization to salivary antigens inoculated in insect bites. It is mainly seen in children. Clinical, aetiological, epidemiological, histophatological and immunological features are considered, as well as prevention and treatment aspects.

Adult↗
PubMed2005

[Recombinant antibodies: a new application in scorpion envenomation?].

Serotherapy is the only specific treatment for envenomation. The antibodies are obtained after the purification of serum from hyperimmunised horses and are used after fragmentation in the form of polyclonal Fab or F(ab)'2. The anti-venom sera are heterogeneous, and their protective effect is often weak. The administration of these preparations induces risks of immediate or delayed side effects: hypersensitivity reactions, anaphylactic shock and serum sickness. This observation led us to develop new forms of antibodies produced by molecular engineering, capable of specifically neutralizing the neurotoxins responsible for the toxicity of the venom of Androctonus australis Hector. The recombinant antibody fragments are more homogeneous than conventional antivenoms and perfectly characterized in terms of specific activity. The method used to obtain them eliminates the risk of transmission by non-conventional transmissible agents. The earliest results confirm the importance of these new molecules (scFv recombinant Fab, diabody, triabody) and their ability to neutralize the action of scorpion neurotoxins. They could open the path to a new generation of more homogeneous antivenoms that are better tolerated and have well-characterized intrinsic properties.

Animals↗
PubMed2005

The Diamond STING server.

Diamond STING is a new version of the STING suite of programs for a comprehensive analysis of a relationship between protein sequence, structure, function and stability. We have added a number of new functionalities by both providing more structure parameters to the STING Database and by improving/expanding the interface for enhanced data handling. The integration among the STING components has also been improved. A new key feature is the ability of the STING server to handle local files containing protein structures (either modeled or not yet deposited to the Protein Data Bank) so that they can be used by the principal STING components: (Java)Protein Dossier ((J)PD) and STING Report. The current capabilities of the new STING version and a couple of biologically relevant applications are described here. We have provided an example where Diamond STING identifies the active site amino acids and folding essential amino acids (both previously determined by experiments) by filtering out all but those residues by selecting the numerical values/ranges for a set of corresponding parameters. This is the fundamental step toward a more interesting endeavor-the prediction of such residues. Diamond STING is freely accessible at http://sms.cbi.cnptia.embrapa.br and http://trantor.bioc.columbia.edu/SMS.

Acid Anhydride Hydrolases↗