CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis

Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.Fil: Blanco-Pérez, Frank. Paul-ehrlich-institut;Fil: Kato, Yoichiro. Tokyo Women's Medical University;Fil: Gonzalez-Menendez, Irene. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Laiño, Jonathan Emiliano. Paul-ehrlich-institut;Fil: Ohbayashi, Masaharu. Toyohashi Sozo University;Fil: Burggraf, Manja. Paul-ehrlich-institut;Fil: Krause, Maren. Paul-ehrlich-institut;Fil: Kirberg, Jörg. Paul-ehrlich-institut;Fil: Iwakura, Yoichiro. Tokyo University Of Science;Fil: Martella, Manuela. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Quintanilla-Martinez, Leticia. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Shibata, Noriyuki. Tokyo Women's Medical University;Fil: Vieths, Stefan. Paul-ehrlich-institut;Fil: Scheurer, Stephan. Paul-ehrlich-institut;Fil: Toda, Masako. Paul-ehrlich-institut; . Tohoku University

Allergenicity assessment of genetically modified crops—what makes sense?

GM crops have great potential to improve food quality, increase harvest yields and decrease dependency on certain chemical pesticides. Before entering the market their safety needs to be scrutinized. This includes a detailed analysis of allergenic risks, as the safety of allergic consumers has high priority. However, not all tests currently being applied to assessing allergenicity have a sound scientific basis. Recent events with transgenic crops reveal the fallacy of applying such tests to GM crops

The Utility of an International Sera Bank for Use in Evaluating the Potential Human Allergenicity of Novel Proteins

In the safety assessment of novel foods produced through biotechnology, careful consideration is given to determining the allergenic potential of newly introduced proteins. IgE serum screening is one tool for evaluating whether the protein in question has sequence identity to a known allergen or if the source of the gene encoding the protein is a known allergenic food. A "specific” serum screen involves testing a gene product with sera from patients with documented clinical allergy to a specific allergen to confirm that the gene product of interest is not the same protein to which the patient produces IgE antibodies. A "targeted” serum screen involves testing the gene product of interest with sera from patients sensitive to food or aeroallergens from the same broad group. The concept of a global sera bank with accessible, well-characterized sera for use in such assays is an appealing option. This paper summarizes the consensus elements from a workshop to evaluate the potential utility of an international sera bank for evaluating the allergenicity of novel proteins. Areas of agreement following the workshop included the following: (1) specific sera screens are appropriate for exploring potentially cross-reactive proteins that have been identified through bioinformatics analyses; however, additional validation is needed, particularly for targeted sera screens, (2) practical and ethical considerations may preclude the formation of a global sera bank, and therefore, (3) a regional network of clinicians who could serve as sources of patient sera or be approached to conduct sera studies would be the most practical alternativ

Does the food ingredient pectin provide a risk for patients allergic to non-specific lipid-transfer proteins?

Pectin, a dietary fiber, is a polysaccharide that is widely used in food industry as a gelling agent. In addition, prebiotic and beneficial immunomodulatory effects of pectin have been demonstrated, leading to increased importance as food supplement. However, as cases of anaphylactic reactions after consumption of pectin-supplemented foods have been reported, the present study aims to evaluate the allergy risk of pectin. This is of particular importance since most of the pectin used in the food industry is extracted from citrus or apple pomace. Both contain several allergens such as non-specific lipid transfer proteins (nsLTPs), known to induce severe allergic reactions, which could impair the use of pectins in nsLTP allergic patients. Therefore, the present study for the first time was performed to analyze residual nsLTP content in two commercial pectins using different detection methods. Results showed the analytical sensitivity was diminished by the pectin structure. Finally, spiking of pectin with allergenic peach nsLTP Pru p 3 led to the conclusion that the potential residual allergen content in both pectins is below the threshold to induce anaphylactic reactions in nsLTP-allergic patients. This data suggests that consumption of the investigated commercial pectin products provides no risk for inducing severe reactions in nsLTP-allergic patients

Identification and molecular characterization of allergenic nsLTP from durum wheat (Triticum turgidum)

Background: Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. Objective: To identify and assess the allergenicity of nsLTP from T. turgidum. Methods: Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. Results: Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Conclusions and Clinical Relevance: Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA

Influence heat-reflective coating on the decrease of heat losses of window constructions

Developed theoretical and methodological foundations of the optimal choice of space-planning and constructive decisions of low-rise buildings blocked type, aimed at improving efficiency of investment, energy and resource saving, creation of comfortable conditions for the population, ensure sustainable development of low-rise construction in the context of socio-economic priorities in the climatic zoning of the area of construction