Biomedical subjects

B Van Esch

Publications and source records attributed to B Van Esch.

9 recordsLinked to original sources

PubMed1998

Involvement of IL-16 in the induction of airway hyper-responsiveness and up-regulation of IgE in a murine model of allergic asthma.

Experiments were designed to investigate the role of IL-16 in a mouse model of allergic asthma. OVA-sensitized mice were repeatedly exposed to OVA or saline aerosols. Bronchoalveolar lavage fluid (BALF) was collected after the last aerosol, and the presence of IL-16 was evaluated using a migration assay with human lymphocytes. Migration of lymphocytes was significantly increased in the presence of cell-free BALF from OVA-challenged mice compared with BALF from saline-challenged controls. This response was significantly inhibited after addition of antibodies to IL-16, demonstrating the presence of IL-16 in BALF of OVA-challenged animals. Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice. IL-16 immunoreactivity was absent in nonsensitized animals; however, some reactivity was detected in epithelial cells of sensitized but saline-challenged mice, suggesting that sensitization induced IL-16 expression in airway epithelium. Treatment of mice with antibodies to IL-16 during the challenge period significantly suppressed up-regulation of OVA-specific IgE in OVA-challenged animals. Furthermore, antibodies to IL-16 significantly inhibited the development of airway hyper-responsiveness after repeated OVA inhalations, whereas the number of eosinophils in bronchoalveolar lavage or airway tissue was not affected. In conclusion, IL-16 immunoreactivity is present in the airways after sensitization. After repeated OVA inhalation, IL-16 immunoreactivity is markedly increased and IL-16 is detectable in BALF. Furthermore, IL-16 plays an important role in airway hyper-responsiveness and up-regulation of IgE but is not important for eosinophil accumulation in a mouse model of allergic asthma.

Animals↗

PubMed1998

Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma.

In the present study, we investigated whether allergen immunotherapy is effective in a murine model with immunologic and pathophysiologic features reminiscent of allergic asthma. Ovalbumin-sensitized mice received increasing (1 microgram to 1 mg) subcutaneous doses of ovalbumin twice a week for 8 wk according to a semirush immunotherapy protocol as used in allergic patients. During immunotherapy, an initial rise in serum levels of ovalbumin-specific antibodies (immunoglobulin [Ig]G1, IgE, IgG2a) occurred, after which IgE levels decreased sharply concomitant with an increase in IgG2a levels. The increase in IgG2a levels, with the decline in IgE levels, suggests that during immunotherapy interferon-gamma production is increased or interleukin (IL)-4 production is decreased. After immunotherapy, inhalation challenge of the mice with ovalbumin revealed almost complete inhibition (98%, P < 0.01) of eosinophil infiltration into bronchoalveolar lavage and airway hyperresponsiveness (100% at 320 microgram/kg methacholine, P < 0.05) compared with sham-treated animals. In addition, IL-4 production of thoracic lymph node cells stimulated with ovalbumin in vitro was largely reduced (60%, P < 0.05) after immunotherapy. Thus, effective immunotherapy in this animal model appears to be due to modulation of antigen-specific T cells. Similar effects on airway symptoms and IL-4 production can be obtained within 1 wk by three injections of the highest dose of ovalbumin (1 mg). This animal model will be used as a preclinical model to improve allergen immunotherapy and to gain more insight into the mechanisms involved.

Alveolitis, Extrinsic Allergic↗

PubMed1997

Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration.

In this study the role of interleukin (IL)4, IL5, interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha in the development of airway hyperresponsiveness and inflammatory cell infiltration was investigated using a murine model for allergic asthma. Mice were sensitized with ovalbumin and subsequently challenged repeatedly with ovalbumin aerosols. During the challenge period, mice were treated with monoclonal antibodies directed against IL4, IL5, IFN gamma, or TNF alpha. Control antibody-treated mice showed airway hyperresponsiveness to methacholine and the presence of eosinophils in bronchoalveolar lavage (BAL). Treatment with antibodies to IFN gamma completely abolished development of airway hyperresponsiveness in ovalbumin-challenged animals. After treatment with antibodies to TNF alpha, airway hyperresponsiveness in the ovalbumin-challenged animals was partially but not significantly inhibited. Antibodies to IL4 or IL5 did not inhibit airway hyperresponsiveness. The presence of eosinophils in BAL of ovalbumin-challenged mice was completely inhibited after treatment with antibodies to IL5. Treatment with antibodies to IL4, IFN gamma, or TNF alpha had no effect on eosinophilia. Because IFN gamma and IL5 have either an effect on the induction of airway hyperresponsiveness or on the development of eosinophil infiltration, our results suggest that the two phenomena are differentially regulated.

Administration, Inhalation↗

PubMed1996

Effect of dexamethasone and endogenous corticosterone on airway hyperresponsiveness and eosinophilia in the mouse.

1. Mice were sensitized by 7 intraperitoneal injections of ovalbumin without adjuvant (10 micrograms in 0.5 ml of sterile saline) on alternate days and after 3 weeks exposed to either ovalbumin (2 mg ml-1 in sterile saline) or saline aerosol for 5 min on 8 consecutive days. One day before the first challenge, animals were injected intraperitoneally on a daily basis with vehicle (0.25 ml sterile saline), dexamethasone (0.5 mg kg-1) or metyrapone (30 mg kg-1). 2. In vehicle-treated ovalbumin-sensitized animals ovalbumin challenge induced a significant increase of airway responsiveness to metacholine both in vitro (27%, P < 0.05) and in vivo (40%, P < 0.05) compared to saline-challenged mice. Virtually no eosinophils could be detected after saline challenge, whereas the numbers of eosinophils were significantly increased (P < 0.01) at both 3 and 24 h after the last ovalbumin challenge (5.48 +/- 3.8 x 10(3) and 9.13 +/- 1.7 x 10(3) cells, respectively). Furthermore, a significant increase in ovalbumin-specific immunoglobulin E level (583 +/- 103 units ml-1, P < 0.05) was observed after ovalbumin challenge compared to saline challenge (201 +/- 38 units ml-1). 3. Plasma corticosterone level was significantly reduced (-92%, P < 0.001) after treatment with metyrapone. Treatment with metyrapone significantly increased eosinophil infiltration (17.4 +/- 9.93 x 10(3) and 18.7 +/- 2.57 x 10(3) cells, P < 0.05 at 3 h and 24 h, respectively) and potentiated airway hyperresponsiveness to methacholine compared to vehicle-treated ovalbumin-challenged animals. Dexamethasone inhibited both in vitro and in vivo hyperresponsiveness as well as antigen-induced infiltration of eosinophils (0, P < 0.05 and 0.7 +/- 0.33 x 10(3) cells, P < 0.05 at 3 h and 24 h, respectively). Metyrapone as well as dexamethasone did not affect the increase in ovalbumin-specific immunoglobulin E levels after ovalbumin challenge (565 +/- 70 units/ml-1; P < 0.05; 552 +/- 48 units ml-1, P < 0.05 respectively). 4. From these data it can be concluded that exogenously applied corticosteroids can inhibit eosinophil infiltration as well as airway hyperresponsiveness. Vise versa, endogenously produced corticosteroids play a down-regulating role on the induction of both eosinophil infiltration and airway hyperresponsiveness.

Animals↗

PubMed1993

Effects of parainfluenza type 3 virus on guinea pig pulmonary alveolar macrophage functions in vitro.

The influence of parainfluenza type 3 (PI-3) virus on the release of inflammatory mediators by guinea pig pulmonary alveolar macrophages (PAMs) was investigated in vitro. Direct application of PI-3 virus dose-dependently stimulated the generation of chemiluminescence by PAMs and induced aggregation of PAMs. No significant effects of PI-3 virus on the release of linoleic acid metabolites by PAMs were detected. However, an increased release of the arachidonic acid metabolite thromboxane B2 (TxB2) was observed when PAMs were stimulated with PI-3 virus. PAMs were also cultured for 2 h or 18 h in the presence of PI-3 virus or control medium. The production of reactive oxygen species and the release of fatty acid metabolites by these PAMs were determined upon stimulation with opsonized zymosan particles or phorbol myristate acetate. The amounts of hydrogen peroxide and superoxide produced did not differ between virus- and control medium-incubated PAMs. However, the PI-3 virus-treated PAMs generated twice as much chemiluminescence when compared to PAMs incubated with control medium. The 2-h incubation period with PI-3 virus also resulted in a decreased release of TxB2 from the PAMs upon zymosan stimulation. The changes in the production of reactive oxygen species and the release of TxB2 by PAMs could account for damage to the airways and bronchial hyperresponsiveness often seen after viral infection.

Animals↗

PubMed1992

Virus-induced airway hyperresponsiveness in guinea pigs in vivo: study of broncho-alveolar cell number and activity.

Recently, we demonstrated that an increased airway responsiveness in vitro can be measured 4, 8, and 16 days, but not 2 days, after intratracheal inoculation of parainfluenza-3 (PI-3) virus to guinea pigs. In the present study airway responsiveness was measured in vivo, and the number, types and activity of broncho-alveolar cells was determined. A significant increase in airflow resistance was measured in spontaneously breathing anesthetized guinea pigs in response to histamine and methacholine, 4 and 8 days after PI-3 virus inoculation. 2 days after inoculation with control solution or PI-3 virus, no difference in the total number of inflammatory cells was observed in the broncho-alveolar lavage fluid. In contrast, on days 4, 8, and 16 after infection a significant increase in the number of alveolar macrophages (102%, 76%, 68%, respectively), monocytes (552%, 374%, 360%, respectively), and lymphocytes (253%, 675%, 396%, respectively) was found. The number of eosinophils was increased as well, but faded with time (378%, 312%, 63%, respectively). PI-3 virus was found to be a very potent activator of broncho-alveolar cells as measured by chemiluminescence. The increase in chemiluminescence production in response to PI-3 virus was reduced in cells obtained from PI-3 virus pretreated animals (day 2, 42%; day 4, 65%; day 8, 22%; and day 16, 30%). In conclusion, PI-3 virus can stimulate broncho-alveolar cells and the virus-induced airway hyperresponsiveness is associated with an influx of inflammatory cells in the respiratory tract.

Airway Resistance↗

PubMed1991

The use of adenovirus-infected HeLa cells for the detection of low titer autoantibodies.

Following infection of HeLa cells with adenovirus type 5 the cellular La protein becomes predominantly associated with the virally encoded RNA polymerase III products VAI, and VAII, while most of the host RNA polymerase II (e.g. U1, U2, U4, U5 and mRNA) and RNA polymerase III transcription (e.g. U6 and pre-tRNAs) ceases. Other RNA polymerase III products such as the cellular Ro RNAs continue to be transcribed and assembled into ribonucleoprotein complexes containing the Ro (SS-A) antigens. Using a 32P-pulse chase-labeled, adenovirus-infected HeLa cellular extract as a source of antigen, anti-La (SS-B) and anti-Ro (SS-A) antibodies can be detected simultaneously using an immunoprecipitation assay. In the present study this method was found to be more sensitive in detecting anti-La antibodies then counter immunoelectrophoresis and immunoblotting. In studies of sera from patients suffering from rheumatic diseases the percentage positive for anti-La antibody was significantly elevated using this method, especially in patients with systemic lupus erythematosus.

Adenoviruses, Human↗

PubMed1990

Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells.

Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed.

Animals↗

PubMed1988

Specific and non-specific effects of beta-adrenoceptor agonists on guinea pig alveolar macrophage function.

The existence of beta-adrenoceptors on guinea pig alveolar macrophage membranes was determined by means of radioligand binding studies. Saturable binding with [125I]cyanopindolol demonstrated 38 +/- 6 fmol binding sites per 10(6) alveolar macrophages with a Kd of 0.85 +/- 0.15 nM. With timolol, atenolol and ICI 118.551 for competition of [125I]cyanopindolol binding it became clear that guinea pig alveolar macrophages possessed adrenergic binding sites of the beta 2-subtype. The cyclic AMP levels of alveolar macrophages could be increased by selective beta 2-adrenoceptor agonists but not by selective beta 1-adrenoceptor agonists. The influence of non-selective beta- and selective beta 1- and beta 2-adrenoceptor agonists on the phagocytic and metabolic responsiveness of alveolar macrophages was also studied. Addition of beta-adrenoceptor agonists had no effect on the uptake of bacteria by alveolar macrophages. Incubation of alveolar macrophages with increasing amounts of non-selective and selective beta 1-agonists resulted in a dose-dependent decrease in the detection of hydrogen peroxide released by alveolar macrophages. This effect was due to the scavenging properties of these drugs. The selective beta 2-receptor agonists, salbutamol and terbutaline, had no effect on the oxidative metabolism of alveolar macrophages. We conclude that guinea pig alveolar macrophages possess beta 2-adrenoceptors on their cell surface and that these receptors are not involved in the phagocytic activity of alveolar macrophages.

Adrenergic beta-Agonists↗