Aspirin does not preferentially potentiate IgE dependent basophil CD63 upregulation in patients with food-dependent exercise-induced anaphylaxis

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Histamine receptor expression on peripheral blood lymphocytes is influenced by specific and nonspecific activation.

Histamine is a physiological mediator which exerts both effector and regulatory functions through its receptors on various cells. The aim of the study was to investigate changes in histamine receptor expression on peripheral blood lymphocytes affected by stimulation with both specific and nonspecific stimuli. Lymphocytes were obtained from both healthy and allergic subjects. Cells were incubated with various allergens (mixed grass pollen, Lolium perenne, Dermatophagoides pteronyssinus 1, bee venom, phospholipase A2) and nonspecific (fMLP, PMA/ionomycin, LPS) stimuli. The percentage of histamine-binding cells was determined with a fluorescence microscope after incubation with histamine-fluorescein. In control subjects histamine binding after stimulation with allergens was not significantly changed. In contrast, in allergic subjects stimulation with specific allergens resulted in significantly increased histamine binding. Nonspecific stimulation caused increased histamine binding to lymphocytes in both allergic subjects and healthy controls. We conclude that specific and nonspecific activation of lymphocytes is associated with increased expression of histamine receptors.

[Effects of anti-inflammatory drugs on adhesion and migration of lymphocytes]. / Wplyw leków przeciwzapalnych na adhezje i migracje limfocytów.

The first crucial step of cell recruitment to the sites of inflammation is adhesion and motility, which are interdependent phenomena. The purpose of our study was investigate the influence used anti-inflammatory drugs (Aspirin, Cyclosporin A, Methotrexate) and endogenous substances of anti-inflammatory activity (Cortisol, TGF-beta) on these phenomena. Lymphocytes from healthy subjects were preincubated with various concentrations of these substances and adhesion to plastic bound CD11a/CD18, CD11c/CD18, CD44 and CD62L mAbs was determined. Simultaneously, cell motility was investigated after Boyden method. We found significant reduction of cell adhesion to all the ligands used. Furthermore we observed significant dose dependent increase in motility of these cells. These data indicate that simultaneous enhancement of motility and reduction of adhesion might be a common pathway for the mechanisms of action of anti-inflammatory agents.

Modulation of adhesion and chemotaxis of human neutrophils by cortisol, transforming growth factor-beta and antiinflammatory drugs.

Neutrophils are the first cells that accumulate in response to stimuli from the arising inflammation site. We have studied the influence of commonly used antiinflammatory (acetylsalicylic acid) and immunosuppressive (cyclosporin A, methotrexate) drugs and endogenous substances of antiinflammatory activity (cortisol, transforming growth factor-beta; TGF-beta) on the interdependent phenomena of cell motility and adhesion. Neutrophils from healthy subjects were preincubated with various concentrations of these substances and adhesion to plastic-bound monoclonal antibodies to CD11a/CD18, CD11c/ CD18 and CD44 was determined. We have found that the studied drugs significantly lowered adhesion (by 40%) of neutrophils to the ligands. Simultaneously, cell motility was investigated according to the Boyden method. We found a significant dose-dependent increase in the motility of this cells in a range comparable to conventional chemoattractants for neutrophils. These data indicate that simultaneous enhancement of motility and reduction of adhesion might be a common pathway for the mechanisms of action of the most common anti-inflammatory drugs.

Spontaneous motility and chemotaxis of neutrophils is influenced by glycocorticosteroid therapy.

The migration of neutrophils is an important part of the allergic inflammatory response. The aim of our study was to investigate the effect of glucocorticosteroids (GCS) on the stimulated and unstimulated migration of neutrophils. The study comprised 103 asthmatics including 44 subjects under GCS therapy (20 GCS resistant and 24 GCS sensitive) as well as 96 healthy control individuals. Unstimulated (random) motility as well as chemotactic response towards fMLP (10-8 mol/l) were determined after Boyden method. Neutrophil motility was determined by the distance of the leading front in filter. In both resistant and sensitive asthmatics under GCS therapy we observed significantly increased unstimulated motility as compared to normal controls (p < 0.001). However, this effect was not demonstrated in the GCS untreated group. Neutrophil chemotaxis towards fMLP was increased in GCS untreated group as compared to healthy controls (p < 0.05). In GCS sensitive subjects the chemotatic activity was decreased. In GCS resistant asthmatics it was moderately increased. We conclude that increased unstimulated neutrophil motility might be one of the immunosuppressive mechanisms of GCS by preventing the cell accumulation at the sites of inflammation.

Effect of hydrocortisone treatment on oxygen metabolism and phagocytosis of peripheral blood neutrophils in asthmatic patients, sensitive and resistant to glucocorticosteroid therapy.

The inflammatory activity of peripheral blood neutrophils of patients suffering from atopic asthma and treated with glucocorticosteroids was investigated. Two tests were performed: 1. chemiluminescence test of neutrophils, and 2. phagocytosis test of latex and bacteria (Staphylococcus aureus 209 P) by neutrophils before and after incubation of the cells with hydrocortisone. The tests were carried out in 3 selected groups of (1) asthmatic steroid sensitive patients, (2) asthmatic steroid resistant patients, and (3) healthy individuals. The neutrophil chemiluminescence stimulation index was found to be significantly lower in the asthmatic steroid sensitive group as compared to the other groups. The index increased in this group after neutrophil incubation with hydrocortisone. The results of phagocytosis of latex by neutrophils before and after their incubation with hydrocortisone were similar in all the 3 groups. The results of phagocytosis of bacteria by neutrophils in the asthmatic steroid sensitive group were significantly lower after incubation of neutrophils with hydrocortisone only.

[A comparative study on skin tests and allergen-specific IgE levels determined by enzyme allergo-sorbent testing (EAST)]. / Badania porównawcze zgodnosci testów skórnych ze stezeniem swoistych prezeciwcial IgE oznaczanych metoda enzyme allergo-sorbent testing (EAST).

Ninety seven randomly selected subjects with bronchial asthma and allergic rhinitis were classified for the comparative studies. The level of allergen specific IgE determined by Enzyme Allergo-Sorbent Testing (EAST) was compared with skin tests. The statistically significant correlation was found for 9 selected allergens. However, the Spearman's rank correlation coefficient values varied largely, depending on a given allergen. They ranged from 0.74 (Dermatophagoides pteronyssinus) to 0.33 (Birch pollen) what might be, in the authors' opinion, a result of Bencard allergens use for skin tests and Kallestad allergens for EAST.

[Effect of bacteria on chemotaxis of peripheral blood lymphocytes from nonatopic asthmatics]. / Wplyw bakterii na chemotaksje limfocytów krwi obwodowej w astmie nieatopowej.

The chemotactic response of peripheral blood lymphocytes from nonatopic asthmatics and healthy subjects in the gradients of various bacterial strains obtained from the airways of the asthmatic patients was investigated. The dominant autologous strains were found to be effective chemoattractants for lymphocytes form the asthmatics. However, none of the bacterial strains investigated in this study induced increased motility of lymphocytes from healthy subjects. These findings might explain the mechanisms of the accumulation of lymphocytes in the airways of nonatopic asthmatics.

Specific allergen stimulates increased motility of peripheral blood lymphocytes and neutrophils from atopics; the effect of specific immunotherapy.

The chemotactic response of peripheral blood lymphocytes and neutrophils from pollinotics and healthy subjects in pollen allergen gradients, before and after specific immunotherapy was investigated using modified Boyden method. It was found that lymphocytes and neutrophils from allergic patients only responded in a chemotactic way in the gradient of the specific allergen. This effect could be demonstrated also in the period when the patients were asymptomatic. Preincubation of the cells with antibodies against human IgE results in abrogation of this effect only in lymphocytes. Specific immunotherapy results in the increased motility of lymphocytes and neutrophils in the gradient of specific allergen just after immunotherapy and significantly decreased motility of these cells during the next exposure to allergen (pollen season) as compared to the values observed in these subjects before immunotherapy. Thus the reactivity of these cells is the dynamic process largely dependent upon exposure to allergen.

Autologous bacteria induce chemotaxis of peripheral blood mononuclear cells (MNC) from non-atopic asthmatics.

The chemotactic response of peripheral blood MNC from healthy subjects and non-atopic asthmatics against the respective pathogen isolated and cultured from sputum of individual patients was investigated. We found that the wide range of concentrations of autologous bacteria induced chemotaxis of MNC from asthmatics but showed no influence on MNC from healthy subjects. This finding might explain the mechanism of lymphocyte accumulation in the lungs of non-atopic asthmatics.

Specific allergen induced motility of peripheral blood mononuclear cells and polymorphonuclear leukocytes in insect sting allergy.

The motility of peripheral blood mononuclear cells (MNC) and polymorphonuclear (PMN) leukocytes from normal and bee venom allergic subjects was investigated by a modified Boyden micropore filter method. The study comprised MNC locomotion in bee venom and histamine gradients and PMN locomotion in bee venom and fMLP gradients. We demonstrated statistically significant increase in MNC and PMN motility towards bee venom in allergic patients group. This effect disappeared after the preincubation of MNC with anti-human IgE antibodies. We observed no such effect in PMN leukocytes. Increased MNC motility in histamine gradient was observed only in control subjects group. Similarly significant increase in PMN locomotion towards fMLP was found in both allergic and control subjects. The results here demonstrated suggest that a specific allergen might be a chemoattractant for peripheral blood MNC and PMN leukocytes from atopics and could be capable to induce non-infectious inflammatory reactions as a result of its interaction with these sensitive cells.

Specific immunotherapy stimulates the binding of histamine H2 receptor antagonist by lymphocytes.

The binding of antagonists of histamine receptors H1 (promethazine) and H2 (ranitidine) by peripheral blood lymphocytes from pollinotics was determined before and after the course of immunotherapy. We found that lymphocytes from atopic subjects showed significant decrease in the binding of H2 receptor antagonist as compared to control subjects. Specific immunotherapy induced statistically significant increase in H2 receptor antagonist binding, which correlated with the improvement of clinical symptoms.

Binding of antagonists of H1 and H2 histamine receptors to peripheral blood lymphocytes of atopic and healthy subjects.

The binding of the antagonists of histamine H1 and H2 receptors by peripheral blood lymphocytes from atopic and healthy subjects was investigated. We found that lymphocytes from atopic subjects showed statistically significant decrease in the binding of H2 receptor antagonist - ranitidine. In addition, lymphocytes from atopic and control subjects had similar capacity of binding of H1 receptor antagonist - promethazine. The ratio of the amount of H1 and H2 antagonists, bound to lymphocytes from atopic and healthy subjects, was calculated. The difference between the values in the group of atopic (2.55) and control subjects (1.55) was statistically significant.

Impaired histamine binding by gastric juice of patients with duodenal ulcer.

Histamine binding by gastric juice from 32 patients with duodenal ulcer and 22 control subjects was tested in vitro. The patients had substantially decreased histamine binding both in basal output as well as in pentagastrin stimulated output. The authors suggest that this phenomenon is involved in etiopathogenesis of chronic ulcer disease.

The effect of immunotherapy in hayfever patients on histamine binding capacity of blood serum proteins.

Binding of histamine (histaminopexy) by blood serum proteins of 16 hayfever patients was determined before and after treatment with Pollinex. An increase in histaminopexy by 83% in comparison to pretreatment value was observed and it was well correlated with the clinical status of the patients. Participation of this phenomenon in the mechanism of therapeutic effect of specific immunotherapy is discussed.

Changes of histaminopexy in patients with bronchial asthma and chronic urticaria after histaglobin administration.

In patients suffering from bronchial asthma and chronic urticaria, the value of histaminopexy was determined prior and after histaglobin treatment (3 injections-1 amp. at 7 days intervals). The value of histaminopexy after histaglobin treatment rised over -240% and was well correlated with the clinical effect of the therapy. These observations are considered as an "ex iuvantibus" evidence that histaminopexy may play a role in the etiopathogenesis of allergic disorders.