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Recent years of research have shed a new light on the role of IgE in immune reactions. It seems to be more than just a contribution to immediate type of allergic response. It appears that monomeric IgE may enhance mast cell activity without cross-linking of FcεRI by IgE specific allergen or autoreactive IgG anti-IgE antibodies. Monomeric IgE molecules are heterogeneous concerning their ability to induce survival and activation of mast cells only by binding the IgE to FcεRI, but not affecting degranulation of cells. It also turned out that IgE may react to autoantigens occurring in the blood not only in chronic spontaneous urticaria (CSU) but also in other autoimmune diseases. The aforementioned phenomena may promote the activity of mast cells/basophils in CSU that easily degranulate when influenced by various inner (autoreactive IgG against IgE and FcεRI, autoreactive IgE for self-antigens) and outer factors (cold, heat, pressure) or allergens. These findings forced the new approach to the role of autoimmunity, self-antigens and IgE autoantibodies in the pathology of CSU. CSU put in the scheme of autoreactive IgG and autoreactive IgE seems to be either a kind of an autoimmune disease or a clinical manifestation of some other defined autoimmune diseases or both.

The aim of the study was to evaluate the sensitivity and specificity of allergen-induced basophil CD164 upregulation in patients with seasonal allergic rhinitis caused by allergy to grass pollens. This study was performed in 24 patients with allergy to grass pollens, and in 25 healthy controls. The protocol for allergen-induced basophil CD164 upregulation consisted of whole blood samples processing and staining with anti-CCR3/anti-CD164 antibodies added to a buffer at the beginning of stimulation. We observed dose-dependent allergen-induced basophil CD164 upregulation with 100% of specificity in both used allergen concentrations (12 and 1.2 ng/ml). Higher allergen concentration resulted in 100% and lower concentration in only 70.83% sensitivity. We have observed in the patients statistically significant correlations between anti-IgE stimulation and both allergen concentrations (for 12 ng/ml, r = 0.71, p < 0.0001; and for 1.2 ng/ml, r = 0.64, p < 0.001). We conclude that assessment of allergen-induced basophil CD164 upregulation is a very useful method for in vitro determination of allergy to grass pollens. This method seems to be a very promising tool in laboratory testing of allergies to other allergens.

Introduction: Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-beta might be a central mediator of tissue fibrosis and remodeling., Materials and Methods: Immunohistochemistry was used to measure collagen III deposition and TGF-beta(1) expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness., Results: Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-beta(1) expression negatively correlated with collagen III deposition and TBM thickness., Conclusions: The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-beta(1) needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

Introduction: Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated., Materials and Methods: One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests., Results: Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25-75% quartiles: 0.6-2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25-75% quartiles: 0.8-2.4 and median: 0.9 mg/l, 25-75% quartiles: 0.5-2.8, respectively; p=0.297). There was no statistically significant correlation (r = -0.163, p = 0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p = 0.22,, Conclusions: Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.

Magnesium deficiency is a common electrolyte disorder in patients with acute severe asthma, but intracellular magnesium content better reflects its homeostasis than does its serum concentration. Magnesium takes part in many metabolic processes in the organism, including energy metabolism, protein and nucleic acid synthesis, cell cycle, the binding of substances to the plasma membrane, and maintenance of cytoskeletal and mitochondrial integrity. It also modulates ion transport and influences intracellular calcium concentration. Maintenance of the cells' transmembrane gradient depends on the presence of magnesium, and hypomagnesemia may result in an increase in neuromuscular cell excitability. Magnesium is a cation modulating the smooth muscle contractility of different tissues: hypomagnesemia causes their contraction and hypermagnesemia their relaxation. Suggestions of a positive influence of magnesium in the treatment of asthma exacerbation have been known for a long time, but research results differ. A single dose of intravenous magnesium sulfate given to patients with acute asthma exacerbation has been shown to be safe, but its efficiency is still under discussion. According to the Global Initiative for Asthma GINA-2005, magnesium sulfate administration is not recommended for routine treatment, but it is permitted in patients with severe asthma exacerbation not responding to treatment (evidence category A). Recommendations of the British Thoracic Society allow one dose of magnesium sulfate to patients with acute severe asthma exacerbation and inadequate initial response to broncho-dilating inhalation treatment (evidence category A). Future investigations should help to establish the indications for magnesium use in the treatment of acute asthma exacerbations as well as the magnesium dose and the scheme of its administration.

Mast cells (MCs) are both central effectors and signaling cells in allergic reactions. Their key role in the immunopathology of asthma and other allergic diseases has been well documented. Molecular events leading to MC activation have not been yet fully established, however. Recent studies emphasize the key role of the protein tyrosine kinases Lyn and Fyn in MC signal transduction. The finding that Lyn kinase negatively regulates MC degranulation and that Fyn kinase enhances this effector response is of great importance. This creates new possibilities for therapeutic intervention in asthma and other allergic diseases. This review summarizes current knowledge on MC intracellular signaling and discusses the most recent strategies for the treatment of allergic diseases based on MC signaling pathway inhibition.

Bronchoalveolar lavage (BAL) or induced sputum (IS) techniques may provide leukocytes for the evaluation of airway inflammatory response in bronchial asthma. The aim of the present study was to compare features of leukocyte populations obtained by the two different methods regarding the cell types and their activity in patients with bronchial asthma. The nitric oxide (NO) level released from the cells was measured as a marker of their activity. Pulmonary leukocytes were obtained from the BAL and IS of 11 asthmatic patients in stable condition at the time of the study. The BAL and IS leukocyte populations varied in cell count and NO production. Macrophages were the predominant leukocyte population in BAL (median (Me) = 83.0%, range 67.9-88.4%), whereas sputum sediments were found to consist mainly of neutrophils (Me = 55.7%, range 29.0-64.9%). The IS leukocytes released much more NO (p = 0.0022) than the BAL leukocytes. In spite of these quantitative differences, a similar pattern of NO production was observed in BAL and in IS cells. Both BAL and IS leukocyte populations produced almost the same amounts of NO before and after lipopolysaccharide stimulation (p = 0.9063, p = 0.4801, respectively). Furthermore, a slight positive correlation Spearman's rank (RS) = 0.5578, p = 0.0594) was noticed between the neutrophil percentages and NO levels produced by BAL cells, whereas in IS a statistically significant correlation between the percentage of neutrophils and the levels of NO (RS = 0.6643, p = 0.0184) was observed. In conclusion, the BAL and IS leukocyte populations are different in cell type, their size and activity. Depending on the asthma severity and the type of cells needed in a study, either BAL or IS specimens may be chosen as a source of pulmonary leukocytes. The use of IS as a noninvasive technique is supposed to be potential value particularly in the study of the airway inflammatory response mediated mainly by neutrophils, i.e. during and/or after exacerbation of the disease. Based on our results, a possible contribution of neutrophils in the production of NO in the airways of asthmatic patients can be proposed apart from other cells such as macrophages.

The aim of the study was to evaluate the activation of eosinophils in an unique case of a young man with atopy manifested as chronic pollen contact urticaria. In order to reveal the role of eosinophils in that case, the study was performed by means of monoclonal antibodies EG2 and chemiluminescence. In addition, comparative electron microscopic study of peripheral blood and skin infiltrating eosinophils were performed for which the name ultrastructural morphometric analysis of intracytoplasmic eosinophil granules has been proposed. The results indicated, that 40% of peripheral blood eosinophils were activated spontaneously and they were more active than those in skin infiltrates. Specific pollen allergen caused activation of 100% of peripheral blood eosinophils. The study suggests presence of a systemic pattern of eosinophil activation in atopy.

Thirteen patients with clinical diagnosis of hay fever, were examined. T lymphocytes subpopulation was determined by the E rosette test. The present study is concerned with the effect of histamine on the ability of T lymphocytes for E rosette formation after blockade of the histamine H2 receptor with its inhibitor cimetidine. It has been found that histamine effect is expressed by the histamine H2 receptor, as its blockade with cimetidine leads to the failure of histamine to inhibit rosette formation by T lymphocytes.

Effect of isoproterenol and propranolol on the production of hemocytotropic antibodies and degranulation of peritoneal mast cells from sensitized mice was studied. It was demonstrated that stimulation with large doses of the antigen caused degranulation of peritoneal mast cells and that additional administration of a beta antagonist propranolol failed to increase the degranulation phenomenon. Marked inhibition in degranulation of mast cells was seen in mice sensitized with large and small doses of antigen after isoproterenol. In 2h PCA test in animals immunized with large doses of the antigen a higher activity of PCA reaction illustrating the concentration of IgG1 antibodies was noted. With higher doses of the antigen and propranolol the titers of the antibodies were markedly higher. The inhibiting effect of isoprenaline on the passive cutaneous anaphylaxis was observed only in the 72 h-test, mostly in the group of mice immunized with small doses of the antigen.

In 20 patients with hay fever and 19 control subjects the rosette formation test was carried out to determine T and B lymphocyte subpopulations. T and B lymphocyte subpopulations are expressed by the percentage of E, EA and EAC rosettes, respectively. Statistical analysis revealed a significant reduction in the number of E rosettes (p < 0.001), and a slight, but statistically significant decrease in the number of EAC rosettes (p < 0.05) in hay fever patients.

Eight persons with clinically diagnosed hay fever were examined. The control group consisted of ten subjects without any signs of allergy. T lymphocyte subpopulation was evaluated by E rosette test. The effect of histamine was studied adding various concentrations of histamine (from 10(-9) to 10(-4) M) to the suspension of lymphocytes. A proportional drop in the percentage of the formed E rosettes could be seen at histamine concentrations ranging between 2 x 10(-9) and 2 x 10(-6) M. At 10(-6) up to 10(-4) M there was both an increase and further reduction in the percentage of the E rosette formation. A question arises whether there exists any correlation between the decreased number of T lymphocytes and elevated content of histamine in atopic persons?