Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis

Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR.

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein [s-ECP] levels as markers of asthma control. A total of 38 children with asthma [16 controlled and 22 partially controlled] were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels [r = -0.60 and -0.75 respectively]. s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control

Evidence for eosinophil degranulation in acute appendicitis.

Finding of increased numbers of eosinophils in the muscle in cases of acute appendicitis has led to the hypothesis that it may have an allergic origin. This study aimed to measure the eosinophil degranulation resulting in a rise in the serum of eosinophil granule proteins that would be expected in such cases. The levels of serum eosinophil cationic protein (ECP) measured by chemiluminescence assay in acute appendicitis were compared, with those of appropriate controls. Mean (95% CI) serum ECP (microg/L) levels were: acute appendicitis 45.3 (27.7-63.0); normal appendix 22.7 (16.0-29.3); asthma 24.2 (4.6-43.8); and healthy volunteers 13.2 (8.3-18.1). In cases of acute appendicitis, there is an inverse relationship between duration of symptoms and serum ECP. However, this was not statistically significant. Significant local eosinophil activation and degranulation occurs in acute appendicitis, enough to cause a rise in serum levels of eosinophil chemotactic protein.

Interrelationship between serum and sputum inflammatory mediators in chronic obstructive pulmonary disease

Little is known about airway inflammatory markers in chronic obstructive pulmonary disease (COPD). The objective of the present study was to identify and try to correlate pulmonary and peripheral blood inflammatory markers in COPD. In a cross-sectional study on patients with stable COPD, induced sputum and blood samples were collected for the determination of C-reactive protein, eosinophilic cationic protein, serum amyloid A protein, a-1 antitrypsin (a-1AT), and neutrophil elastase. Twenty-two patients were divided into two groups according to post-bronchodilator forced expiratory volume in the first second ( percentFEV1): group 1 (N = 12, FEV1 <40 percent) and group 2 (N = 10, FEV1 ³40 percent). An increase in serum elastase, eosinophilic cationic protein and a-1AT was observed in serum markers in both groups. Cytology revealed the same total number of cells in groups 1 and 2. There was a significantly higher number of neutrophils in group 1 compared to group 2 (P < 0.05). No difference in eosinophils or macrophages was observed between groups. Serum elastase was positively correlated with serum a-1AT (group 1, r = 0.81, P < 0.002 and group 2, r = 0.83, P < 0.17) and negatively correlated with FEV1 (r = -0.85, P < 0.03 and -0.14, P < 0.85, respectively). The results indicate the presence of chronic and persistent pulmonary inflammation in stable patients with COPD. Induced sputum permitted the demonstration of the existence of a subpopulation of cells in which neutrophils predominated. The serum concentration of all inflammatory markers did not correlate with the pulmonary functional impairment.

Serum eosinophil cationic protein level and disease activity in childhood rhinitis.

In order to investigate clinical markers of disease activity in childhood rhinitis, we compared various laboratory parameters to symptom scores of children with allergic rhinitis and non-allergic rhinitis. We measured the levels of serum total IgE, aeroallergen specific IgE, serum eosinophil cationic protein (ECP), and blood eosinophil counts in 71 children with allergic rhinitis and in 62 children with non-allergic rhinitis. We found a statistically significant difference in peripheral blood eosinophil counts between the allergic rhinitis and non-allergic rhinitis groups. Serum ECP levels were positively related to symptom scores in both groups. Peripheral blood eosinophil counts correlated with symptom scores only in the group with non-allergic rhinitis. The results demonstrated that serum ECP levels are of value in assessing disease activity in both allergic and non-allergic rhinitis, and peripheral blood eosinophil counts may play a role in the evaluation of symptom severity in non-allergic rhinitis.

Chemokine receptor 3 and eosinophilir cationic protein: as novel laboratoyt markers for assessment of airway inflammation in bronchial asthma

The aim of this work was to trace and follow up the profile of the chemokine receptor3 [CXCR3], eosinophilic cationic protein [ECP] and immunoglobulin E [IgE] in atopic asthmatic patients during and between the attacks and to outline their relations to other parameters denoting disease activity and severity. Moreover, this study also aimed at testing the ability of the three markers to monitor the patients response to treatment in order to tailor relevant therapeutic modalities to alleviate the patients' allergic condition. Thirty seven atopic asthmatic patients [Group 1] were enrolled in this study. They were sub classified according to their peak expiratory flow [PEF] into mild, moderate and severe asthmatics [subgroups IA, IB and IC, respectively]. Their results were compared to those of 13 healthy subjects [Group II]. For all subjects; number of eosinophils in peripheral blood, serum total lgE, serum ECP and plasma CXCRJ% expression by flow cytometry were estimated. For group I only laboratory parameters and PEF were done twice; during acute asthmatic attack and between the attacks [controlled condition after one week of efficient treatment of corticosteroids and supportive therapy]. Highly significant results were found in asthmatic patients' group [Group I] during the attack regarding the number of eosinophils, ECP values and CXCR3% [decrease], while only a significant difference was found regarding IgE levels when compared to healthy controls [Group II]. Comparative study between patients' subgroups was done revealing highly significant differences for patients in subgroups IB and IC regarding CXCR3%, ECP and IgE [in subgroup IC only], when compared to control group. While, in subgroup IA highly significant difference was found regarding ECP values and significant differences were found regarding.. CXCR3% [decrease] and IgE values when compared to controls. Similar results were found when patients subgroups results were compared to each others. Paired t test was used to compare patients' results during acute attack and between attacks [after treatment] to monitor the inflammatory events in both situations, where highly significant differences were found regarding CXCR3% [increase] and ECP levels [decrease], while only a significant difference was found for IgE levels [decrease]. Correlation matrix was performed for patients' results during acute attack revealing strong negative correlations between CXCR3% expression and ECP, IgE and number of eosinophils in peripheral blood [r= -0.8, -0.7 and -0.5, respectively]. While, ECP values had strong positive correlation with IgE [r=0.7] and a weak positive correlation with number of eosinophils in peripheral blood [r= 0.4]. Stepwise multi regression analysis was done to choose the best parameter [s] which can be used for monitoring patients' good response to treatment, where both CXCR3 and ECP were found to be the best for that purpose [F=7.8, p<0.01]. One way analysis of variance [ANOVA] testing and positive likelihood ratio were done to choose the best parameter [s] which can discriminate patients with severe asthma among other asthmatics. ANOVA test revealed that CXCR3% was the best for this purpose [F=47.2, p<0.01] followed by ECP, lgE and number of eosinophuls in peripheral blood [p<0.01, <0.01 and <0.05, respectively]. Moreover, positive likelihood ratio revealed that both CXCR3% and ECP had comparable excellent ratios [ratio =10, respectively] followed by IgE [ratio=7]. This study revealed an integrated explanation of the immunoinflammatory events in acute atopic asthma. Where, a drop of CXCR3 expression paves the way for the immediate hypersensitivity reaction of allergy including T helper2 [Th2] cells with their chemokine receptors leading to eosinophilic recruitment and degranulation releasing ECP with the help of IgE bound on their cell surface resulting in airway inflammatory response and typical allergic reaction of asthma. Hence, new therapeutic modalities for asthmatic patients should include agonists for CXCR3 or Th2 antagonists to alleviate the patient's condition. Moreover, this study demonstrated that short term oral corticosteroids modulate the balance of chemokine receptors' expression in favor of CXCR3 in asthmatic patients. In addition, this work provides evidence that CXCR3 and ECP assays can be used efficiently for monitoring of treatment efficacy in such patients. Lastly, CXCR3, ECP and to a lesser extent IgE assays were found to be good prognostic markers to distinguish patients with severe asthma among other asthmatic patients