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Biomedical subjects

H J Mengelers

Publications and source records attributed to H J Mengelers.

10 recordsLinked to original sources
PubMed1995

Cognate interaction between human lymphocytes and eosinophils is mediated by beta 2-integrins and very late antigen-4.

Here the cognate interactions between human eosinophils and lymphocytes are studied. These interactions were measured in a double-colored FACS analysis by applying fluorescent red eosinophils (stained with hydroethidine, 40 mumol/L) and fluorescent green lymphocytes (stained with sulfidofluorescein diacetate, 100 mumol/L) in a ratio of 1:3. When normal eosinophils were mixed with a total lymphocyte preparation in stirred suspensions (37 degrees C), no physical interaction was present between both cell types. However, the addition of phytohemagglutinin and PMA resulted in a clear aggregation response between both cell types (up to 30% of the eosinophils interacted with lymphocytes after 15 minutes). CD8(+)- and CD4(+)-positive T cells contributed equally to the heterotypic aggregation response. It is interesting that when lymphocytes were pretreated with phytohemagglutinin or eosinophils with phorbol myristate acetate and subsequently washed, the cells still interacted with unstimulated counterparts. The heterotypic interaction between lymphocytes and eosinophils is blocked by monoclonal antibodies directed against the beta-chain of the beta 2-integrins (CLB LFA1/1; CD18) and the alpha-chain of very late antigen-4 (VLA-4) (HP2/1; CD49d), indicating that both the beta 2-integrins and VLA-4 contributed to this heterotypic interaction. When eosinophils bound to PHA-treated lymphocytes, the cells exhibited an activated phenotype that was characterized by an enhanced expression of CD66b and CD11b. The cells interacted with each other provided that an intact cellular metabolism was present--that is, no interaction was seen after treatment with the glycolysis inhibitor sodium mono-iodoacetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1994

Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics.

Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma have demonstrated active migration of eosinophils into the bronchial lumen after allergen challenge. The mechanisms mediating this eosinophil infiltration and cell activation are largely unexplained. The expression of several cell-surface molecules was measured on eosinophils derived from blood and BAL fluid 4 h after an allergen-induced early asthmatic reaction in order to find indications for a role of these molecules during extravasation to and activation in the bronchial compartment. Nine patients with allergic asthma participated in the study. An eosinophil-specific, high-depolarization signal enabled us to measure expression on eosinophils in a fluorescence activated cell sorter (FACS) analysis without isolation of these cells. Eosinophils recovered from BAL showed a different phenotype than blood eosinophils; upregulation of CR-3, p150/95, CD67, and CD63, and downregulation of L-selectin indicate that the cells are activated in terms of degranulation. Up-regulation of intercellular adhesion molecule-1 (ICAM-1), LFA-3, and human leukocyte antigen II (HLA-II) might enable cell-cell contact between T-lymphocytes and eosinophils, probably leading to immunomodulation and cell activation. The finding that eosinophils in BAL are activated and can interact with T cells is further evidence for the proinflammatory role of these cells in allergic asthma.

Adult↗
PubMed1993

Inhibition of cytokine-primed eosinophil chemotaxis by nedocromil sodium.

BACKGROUND: Eosinophil influx into the lung tissue is considered to be relevant for the pathogenesis of asthma. Various chemotactic factors may be responsible for this influx. Recently it has been demonstrated that the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5) are present in the circulation of individuals with allergic asthma. These cytokines have the capacity to modulate chemotactic responses of eosinophils toward platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, (FMLP) and neutrophil-activating factor (NAF)/IL-8, but not toward complement fragment C5a (C5a). Here the effect of nedocromil sodium on the chemotactic response of eosinophils from allergic asthmatic individuals and from normal donors preincubated with GM-CSF or IL-3 toward FMLP, NAF/IL-8 was evaluated. RESULTS: Nedocromil sodium inhibited the chemotactic response toward FMLP and NAF/IL-8 of GM-CSF primed eosinophils approximately 60% (inhibitory concentration of 50% [IC50] approximately 1 to 10 nmol/L), whereas these responses of IL-3 primed eosinophils was completely inhibited (IC50 approximately 1 nmol/L). CONCLUSIONS: The chemotactic responses toward C5a were inhibited by nedocromil sodium at higher concentrations than were required in the priming studies (IC50 approximately 10 to 100 nmol/L). Nedocromil sodium (0.1 mumol/L) was also effective in inhibiting the chemotactic response toward FMLP (10 nmol/L) of eosinophils isolated from the circulation of patients with allergic asthma 3 hours after allergen challenge. These findings might explain in part the antiinflammatory action of nedocromil sodium.

Adult↗
PubMed1993

Upregulation of formyl-peptide and interleukin-8-induced eosinophil chemotaxis in patients with allergic asthma.

BACKGROUND: The cytokine granulocyte-macrophage colony-stimulating factors, interleukin-3 and interleukin-5, are important modulators of eosinophilia and eosinophil function. In particular, eosinophil chemotaxis is very sensitive to cytokine priming. METHODS: We evaluated chemotactic responses of eosinophils from patients with allergic asthma. These cells exhibited a primed phenotype as deduced from enhanced responses toward formyl-methionyl-leucyl-phenylalanine and platelet-activating factor and a decreased responsiveness toward granulocyte-macrophage colony-stimulating factor. Bronchoprovocation of patients with allergic asthma with allergen was performed as a possible means to enhance in vivo priming. RESULTS: Indeed, eosinophils isolated 3 hours after allergen challenge exhibited a more pronounced primed phenotype, which was reflected by an induction of responsiveness towards interleukin-8. Eosinophil responses induced by platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, complement fragment C5a, interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly altered after allergen challenge. CONCLUSION: These data provide further evidence that eosinophils are already primed in the peripheral blood of individuals with allergic asthma. This is most likely due to the presence of circulating cytokines in the peripheral blood of those individuals. This in vivo priming results in selective upregulation and downregulation of responses toward various chemotaxins, which may be released in the lungs during allergic inflammation.

Adult↗
PubMed1993

Down modulation of L-Selectin expression on eosinophils recovered from bronchoalveolar lavage fluid after allergen provocation.

In allergic asthma eosinophils infiltrate into the lung after allergen challenge. The mechanism of this cellular infiltration is not fully understood. L-Selectin is involved in leucocyte-endothelial cell recognition and participates in homing of leucocytes into sites of inflammation. To find indications for a role of L-Selectin in the migration of eosinophils to the bronchoalveolar space we measured L-Selectin expression on eosinophils in peripheral blood and bronchoalveolar lavage fluid (BAL) 4 hr after the early allergic reaction after allergen challenge. Nine patients with allergic asthma participated in the study. An eosinophil specific high depolarization signal enabled us to measure L-Selectin expression on eosinophils in a FACS analysis without isolation of these cells. Eosinophils recovered from BAL showed a strong decrease of L-Selectin expression compared to blood eosinophils. This decrease in L-Selectin expression can be induced in vitro by activation of eosinophils with PMA or FMLP whereas priming of eosinophils during several hours with GM-CSF did not influence L-Selectin expression. Our results are a first indication that L-Selectin may play a role during homing of eosinophils in the lung in asthma after allergen challenge. Moreover, the low expression of L-Selectin on eosinophils in the lung is a further indication that these cells exhibit an activated phenotype.

Adult↗
PubMed1993

Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction.

The administration of platelet-activating factor (PAF) to human subjects triggers asthma-like responses. We investigated whether a bronchoconstrictive reaction was accompanied by the release of PAF in the circulation of allergic asthmatics. The appearance of PAF was assessed by measuring the number of freely accessible PAF-receptors on platelets in vitro, assuming that the contact between platelets and PAF in vivo would reduce the receptor binding of [3H]PAF in vitro. 16 asthmatics were challenged twice, first with buffer and the next day with allergen. A comparison between receptor binding after provocation with the data of the same patients after allergen challenge revealed a significant difference in PAF binding (P = 0.034), with an average decrease of 14% immediately after allergen challenge followed by a return to control values after about 4 h and a transient increase of 9% at 7 h after provocation. The decrease in accessible PAF receptors was accompanied by a slight decrease in platelet count in peripheral blood between 30 min and 4 h after allergen challenge. The platelet counts recovered to the original values afterwards. These data support the concept that in patients with allergic asthma PAF is secreted in the circulation. The contact between PAF and the platelets may trigger the transient sequestration of platelets, possibly in the lung. Thus, PAF and platelets may contribute to the pathogenesis of allergic asthma.

Adolescent↗
PubMed1992

A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.

BACKGROUND: The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. METHODS: In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. RESULTS: Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. CONCLUSIONS: The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Administration, Inhalation↗
PubMed1992

In vivo priming of platelet-activating factor-induced eosinophil chemotaxis in allergic asthmatic individuals.

The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 are important modulators of eosinophilia and eosinophil function. Eosinophil chemotaxis is known to be particularly sensitive for cytokine priming. In the present study, we compared chemotactic responses of eosinophils derived from peripheral blood of allergic asthmatics to responses of eosinophils from peripheral blood of healthy individuals. Eosinophils from allergic asthmatics exhibited a markedly increased sensitivity in their chemotactic response toward platelet-activating factor (PAF) compared with eosinophils from normal donors. In contrast, C5a-induced eosinophil chemotaxis between both groups was similar. This in vivo-primed phenotype could be mimicked in vitro, by preincubating eosinophils from peripheral blood of healthy individuals with picomolar concentrations of either GM-CSF, IL-3, or IL-5. The chemotactic response of eosinophils derived from the circulation of allergic asthmatic patients toward GM-CSF was significantly lower compared with the response of eosinophils of healthy individuals. Our data strongly suggest that release of cytokines may be an important in vivo priming mechanism for eosinophils in the circulation of allergic asthmatic patients. Such an in vivo priming can subsequently result in selective upregulation and downregulation of chemotactic responses toward various chemoattractants release in the lung tissue.

Asthma↗
PubMed1992

Cloning of T lymphocytes from bronchoalveolar lavage fluid.

We have prepared T-cell clones from bronchoalveolar lavage fluid (BALF) from four healthy, nonsmoking persons and from four patients with allergic asthma. T cells were cloned by direct limiting dilution and with the use of a fluorescent activated cell sorter with an automated cell deposition unit. T-cell clones from the blood (PB) were prepared as well. The cloning efficiencies of T cells from BALF ranged from 3 to 40% and were lower than those obtained from PB T cells (18 to 72%). The cloning conditions generated CD4+ as well as CD8+ clones. The very late antigen-4, VLA-4, was more frequently expressed on CD4+ T-cell clones from BALF than from the blood (P < 0.05). CD8+ clones from BALF were more frequently VLA-1+ than those from blood (P < < 0.01). Mitogen- and monoclonal antibody-driven proliferation of CD4+ clones showed that BALF clones were well responsive to proliferation stimuli similar to those from the blood. Analysis of interleukin-4 production by 10 BALF and 10 PB clones showed large variations between individual CD4+ clones (BALF: range, < 100 to 700 pg/ml; PB: range, < 100 to 1,100 pg/ml), indicating the generation of different types of clones, which was also clear from analysis of interferon-gamma production. The analysis of properties of BALF T-cell clones and their regulation will improve insight into immunologic reactions in the lungs.

Adult↗