Close-up of the immunogenic α1,3-galactose epitope as defined by a monoclonal chimeric immunoglobulin E and human serum using saturation transfer difference (STD) NMR

Anaphylaxis mediated by carbohydrate structures is a controversially discussed phenomenon. Nevertheless, IgE with specificity for the xenotransplantation antigen α1,3-Gal (α-Gal) are associated with a delayed type of anaphylaxis, providing evidence for the clinical relevance of carbohydrate epitopes in allergy. The aim of this study was to dissect immunoreactivity, interaction, and fine epitope of α-Gal-specific antibodies to obtain insights into the recognition of carbohydrate epitopes by IgE antibodies and their consequences on a molecular and cellular level. The antigen binding moiety of an α-Gal-specific murine IgM antibody was employed to construct chimeric IgE and IgG antibodies. Reactivity and specificity of the resulting antibodies were assessed by means of ELISA and receptor binding studies. Using defined carbohydrates, interaction of the IgE and human serum was assessed by mediator release assays, surface plasmon resonance (SPR), and saturation transfer difference NMR analyses. The α-Gal-specific chimeric IgE and IgG antibodies were proven functional regarding interaction with antigen and Fc receptors. SPR measurements demonstrated affinities in the micromolar range. In contrast to a reference antibody, anti-Gal IgE did not induce mediator release, potentially reflecting the delayed type of anaphylaxis. The α1,3-Gal epitope fine structures of both the recombinant IgE and affinity-purified serum were defined by saturation transfer difference NMR, revealing similar contributions of carbohydrate residues and participation of both galactose residues in interaction. The antibodies generated here constitute the principle underlying α1,3-Gal-mediated anaphylaxis. The complementary data of affinity and fine specificity may help to elucidate the recognition of carbohydrates by the adaptive immune response and the molecular requirements of carbohydrate-based anaphylaxis.     

Comparison of mucosal adhesion and species identification of bifidobacteria isolated from healthy and allergic infants

Fifty bifidobacteria strains were isolated from fecal samples of allergic and age matched healthy infants. Allergic infants were found to have an adult type Bifidobacterium flora with high levels of Bifidobacterium adolescentis. Healthy infants had a typical infant Bifidobacterium flora with high levels of Bifidobacterium bifidum. These isolates were tested for their adhesive properties to human intestinal mucus. The adhesion of the fecal bifidobacteria from healthy infants was significantly higher (P<0.0001) than for allergic infants. This suggests a correlation between allergic disease and the composition of the intestinal bifidobacteria flora which has reduced adhesive abilities to the intestinal mucus. Therefore, dietary supplementation of bifidobacteria typical for healthy infants, may be beneficial in the treatment of allergic disorders.     

Histone Deacetylase-3 Mediates Positive Feedback Relationship between Anaphylaxis and Tumor Metastasis

Allergic inflammation has been known to enhance the metastatic potential of tumor cells. The role of histone deacetylase-3 (HDAC3) in allergic skin inflammation was reported. We investigated HDAC3 involvement in the allergic inflammation-promotion of metastatic potential of tumor cells. Passive systemic anaphylaxis (PSA) induced HDAC3 expression and FcϵRI signaling in BALB/c mice. PSA enhanced the tumorigenic and metastatic potential of mouse melanoma cells in HDAC3- and monocyte chemoattractant protein 1-(MCP1)-dependent manner. The PSA-mediated enhancement of metastatic potential involved the induction of HDAC3, MCP1, and CD11b (a macrophage marker) expression in the lung tumor tissues. We examined an interaction between anaphylaxis and tumor growth and metastasis at the molecular level. Conditioned medium from antigen-stimulated bone marrow-derived mouse mast cell cultures induced the expression of HDAC3, MCP1, and CCR2, a receptor for MCP1, in B16F1 mouse melanoma cells and enhanced migration and invasion potential of B16F1 cells. The conditioned medium from B16F10 cultures induced the activation of FcϵRI signaling in lung mast cells in an HDAC3-dependent manner. FcϵRI signaling was observed in lung tumors derived from B16F10 cells. Target scan analysis predicted HDAC3 to be as a target of miR-384, and miR-384 and HDAC3 were found to form a feedback regulatory loop. miR-384, which is decreased by PSA, negatively regulated HDAC3 expression, allergic inflammation, and the positive feedback regulatory loop between anaphylaxis and tumor metastasis. We show the miR-384/HDAC3 feedback loop to be a novel regulator of the positive feedback relationship between anaphylaxis and tumor metastasis.     

Effectiveness of benzyl benzoate in elimination of house dust mites

The effect of elimination treatment with benzyl benzoate was examined in 30 adults with asthma caused by sensitivity to house dust mites. The patients were randomised into a control and an active group, who treated their mattresses with benzyl benzoate (Acarosan^®). The study lasted 12 months and the effect of the treatment was monitored by monthly dust sampling, analyzed for major allergens fromDermatophagoides pteronyssinus andfarinae by the ELISA method and for guanine by the Acarex^® method. The clinical effect was assessed by measuring lung function, daily peak flows, symptoms and medicine consumption as well as skin prick tests, and specific IgE to mite allergens. For both groups, a significant decrease was observed in house dust mite allergens, but there was no significant difference between the groups. No considerable differences were observed in clinical parameters within or between the groups. A good correlation was observed between ELISA and Acarex^®. but the latter showed a major variation in the different classes. In conclusion. treatment of mattresses with benzyl benzoate had no effect in a group of patients with asthma due to house dust mite allergy. Regular vacuum cleaning of the bed may reduce house dust mite allergen exposure.     

Cupressaceae pollen in the atmosphere of Ascoli Piceno (Central Italy) and sensitization of allergic subjects

The aim of this work is to study the incidence of pollinosis in the Health District of Ascoli Piceno, Central Italy (U.S.L.24). this being an underestimated pathology from the clinical point of view and also as a result of the recent introduction of this taxa in the National Aeroallergen Network. Since 1990, 5055 patients of both sexes with respiratory symptomatology of suspected IgE mediated aetiology have been examined in our Centre with the Skin Prick Test (SPT) using allergen panels including Cypress; 171 (3.38%) patients were found to be positive to this allergen. These results show that the subjects with symptoms in the period January–March in most cases have a sensitization toCupressus pollen and new studies will evaluate the possibility of specific immunotherapy.     

Suppressor factor from tumor-allosensitized spleen cells--its effect on in vitro proliferation of tumor cells and in vivo skin allograft survival

C57BL/6 mice are sensitized ip with allogeneic P-815 mastocytoma cells. Fifteen days later the spleen cells of the sensitized mice are used in the production of suppressor factor or treated with mitomycin and used as suppressor cells. Sensitized spleen cells incubated with the specific alloantigen (DBA/2 m-treated spleen cells) release suppressor factor (SF)² which inhibits cell proliferation in mixed lymphocyte culture (MLC) as well as the in vitro generation of cytotoxic cells (CML). SF is most effective when added eary during MLC. SF also inhibits mitogen responsiveness of normal spleen cells. In addition to inhibiting lymphocyte function in vitro, suppressor cells as well as SF inhibit the in vitro proliferation of tumor cells. This inhibition is specific for the tumor to which the suppressor cells are induced. The inhibition of tumor cell proliferation is not due to the presence of cytotoxic cells in the spleen of the tumor-allosensitized mice. Suppressor cells from neonatal mice do not inhibit the in vitro proliferation of tumor cells. SF injected iv into C57BL/6 mice decreases the mixed lymphocyte reactivity of the host spleen cells and decreases the ability of the host to reject skin allografts. We interpret these data to suggest that tumor-allosensitized spleen cells, and the SF they produce, not only affect lymphocyte function but also inhibit tumor cell proliferation. This dual effect of suppressor cells could be an important part of the immune surveillance against tumors.     

Protein phosphorylation in anti-actin IgG and [(IgG)2protein A]2 complex-stimulated L cells

Phosphorylation of cellular proteins was stimulated in a dose-dependent manner by the surface binding of IgG antibodies to antigens on L cells. Most prominent among the phosphorylated cellular proteins were Mr = 115,000, 93,000, 58,000, 38,000, and 33,000 proteins. Stimulation of protein phosphorylation was maximal at 48 hr of incubation and was preceeded by maximal stimulated uridine incorporation into RNA (0-24 hr) and thymidine incorporation into DNA (24-48 hr), and followed by maximal stimulated cell proliferation occurring at 72 hr (P less than 0.001 for all differences). Modification of the ligand IgG molecule by formation of complexes with protein A (PA) altered the stimulation patterns of protein phosphorylation: [(IgG)2(PA)]2, Mr = 716,000, enhanced and (IgG)(PA), Mr = 200,000, inhibited phosphorylation. The nature of the cell surface antigen(s) was partially clarified by the demonstration that affinity-purified antibodies to cytoskeletal proteins (principally a surface actin molecule) accounted for a significant part of the stimulation effect. Thus, perturbation of the L-cell membrane by certain molecular forms of anti-actin IgG antibody produces a transmembrane signal resulting in an orderly series of metabolic events including enhanced protein phosphorylation at 48 hr occurring just prior to enhanced cell growth.     

广西南宁空气中孢粉及其致敏性研究

本文通过空气中的孢粉调查,选用32种花粉对呼吸道过敏患者进行皮肤敏感试验,既阐明了南宁市空气中孢粉散布的基本规律,讨论空气中花粉含量与气候的关系,也明确了该市主要致敏花粉是蒿属、禾本科、藜科及桑科植物的花粉,为呼吸道过敏性疾病的预防、诊断及治疗提供了重要依据。     

Aerobiological monitoring ofAlternaria fungal spores: a comparison between surveys in 1992 and 1993 and local meteorological conditions

A study of airborneAlternaria spores was carried out over the period from April 1992 to October 1993, in the Rehabilitation Medical Centre of Montescano (PV), using an automatic volumetric spore trap (VPPS 2000 Lanzoni). The evaluation of the air concentration of these spores is becoming ever more important as it is this mycophyte which is the commonest cause of a positive allergy test. In 1993 the concentration ofAlternaria spores was much higher than in the previous year and the period of highest sporulation was different, depending on the different rainfall pattern of the 2 years.