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See detailDual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
Joos, G. F.; Vincken, W.; Louis, Renaud ULg et al

in European Respiratory Journal (2004), 23(1), 76-81

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the ... [more ▼]

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled crossover trial. Increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol(.)mL(-1)) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log(10) provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log(10) mol(.)mL(-1) at 1 h after DNK333 treatment and -6.8 log(10) mol(.)mL(-1) after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma. [less ▲]

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See detailPathogenic role of matrix metalloproteases and their inhibitors in asthma and chronic obstructive pulmonary disease and therapeutic relevance of matrix metalloproteases inhibitors
Cataldo, Didier ULg; Guéders, Maud ULg; Rocks, Natacha ULg et al

in Cellular and Molecular Biology (2003), 49(6), 875-884

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary ... [more ▼]

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are diseases associated with an inflammation of the airways and lung parenchyma. In this review, we focus on the role played by MMPs in the pathogenesis of inflammation, airway remodelling and alveolar destruction, depicting the observational studies in humans and the experimental studies in animal models. During the course of asthma, MM P-2,-8,-9 and TIMP-1 are expressed at baseline and the allergen exposure or exacerbations of the disease lead to an increase of MMP-9 secretion being at this time much higher than that of TIMP-1, allowing temporarily a matrix damage, possibly followed by abnormal repair. Animal models suggest a predominant role for MMP-9 and MMP-12 in the pathogenesis of pulmonary inflammation and link an absence of MMP-2 to an increased parenchymal inflammation. In COPD and emphysema, human studies indicate an over-secretion of MMP-2,-8,-9 and animal models point out MMP-1 and MMP-12 as being key players in the pathogenesis of emphysema. Taken together, these data identify specific MW inhibition as appropriate target for therapeutic intervention in asthma or COPD/emphysema. They also strongly argue against the widespread use of large spectrum non specific inhibitors that could be detrimental. [less ▲]

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See detailMatrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma
Vermaelen, K. Y.; Cataldo, Didier ULg; Tournoy, K. et al

in Journal of Immunology (2003), 171(2), 1016-1022

Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement ... [more ▼]

Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement membranes. This study investigated the role of MMP-9 in airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion affected the trafficking of pulmonary DCs in a specific way: only the inflammatory transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport of airway Ag to the thoracic lymph nodes remained unaffected. In parallel, the local production of the Th2-attracting chemokine CC chemokine ligand 17/thymus and activation-regulated chemokine, which was highly concentrated in purified lung DCs, fell short in the airways of allergen-exposed MMP-9(-/-) mice. This was accompanied by markedly reduced peribronchial eosinophilic infiltrates and impaired allergen-specific IgE production. We conclude that the specific absence of MMP-9 activity inhibits the development of allergic airway inflammation by impairing the recruitment of DCs into the airways and the local production of DC-derived proallergic chemokines. [less ▲]

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See detailLa vaccination a base de mycobacteries: vaincra-t-elle les allergies?
Louis, Renaud ULg

in Revue Médicale de Liège (2003), 58(6), 392-5

In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while ... [more ▼]

In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while it features a Th2 pattern in allergy. Vaccination with BCG in early life is associated with a reduction in the prevalence of allergy later in childhood. In an experimental mouse model of asthma, administration of BCG or killed Mycobacterium vaccae inhibits the sensitisation process as well as the bronchial inflammation and hyperresponsiveness that follows allergen exposure. In children and adolescents suffering from atopic dermatitis, subcutaneous injection of killed Mycobacterium vaccae attenuates the severity of skin lesions. [less ▲]

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See detailOzone et asthme: un couple dans l'air du temps
Kleis, S.; Louis, Renaud ULg; Bartsch, Pierre ULg

in Revue Médicale de Liège (2003), 58(3), 132-8

Ozone is a pollutant the production of which depends on weather conditions and car engine combustion. Numerous epidemiological studies have indicated that high ozone levels correlated with morbidity in ... [more ▼]

Ozone is a pollutant the production of which depends on weather conditions and car engine combustion. Numerous epidemiological studies have indicated that high ozone levels correlated with morbidity in asthma. Experimental studies have shown that exposure of healthy subjects and asthmatics to ozone levels comparable to those measured in ambient air during hot summer days can generate respiratory symptoms, neutrophilic airways inflammation and lung function impairment. Lung function changes following ozone exposure are more pronounced in asthmatics and are dependent on the duration and intensity of exposure, a previous exposure and the nutritional status of the subjects. The airway epithelial cell layer is likely to play a pivotal role in initiating the inflammatory process following ozone exposure. Control of ambient air ozone levels must be a target for public health authorities. [less ▲]

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See detailInduced sputum studies in asthma
LOUIS, Renaud ULg; Chanez, P

in Djukanovic, Ratko; Sterk, Peter J. (Eds.) An Atlas of INDUCED SPUTUM : an Aid for Research and Diagnosis. (2003)

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See detailInteret des expectorations induites dans l'exploration de l'asthme.
Louis, Renaud ULg; Bettiol, Jane; Cataldo, Didier ULg et al

in Revue des Maladies Respiratoires (2003), 20(2 Pt 1), 215-23

INTRODUCTION: The technique of induced expectoration generates sputum by the inhalation of hypertonic saline. On account of its non-invasive character, its simplicity, its relative harmlessness, its cost ... [more ▼]

INTRODUCTION: The technique of induced expectoration generates sputum by the inhalation of hypertonic saline. On account of its non-invasive character, its simplicity, its relative harmlessness, its cost effectiveness and its reproducibility this technique, that appeared in the early 1990's, has rapidly established itself as the technique of choice in the investigation of bronchial inflammation in asthma. STATE OF THE ART: We present the results of our studies that have contributed to the validation of the technique at the methodological level and to the exploitation of the cellular contents as much as the fluid phase of the expectorations in characterising bronchial inflammation in asthmatics. Our results confirm an infiltration of the airways of asthmatics with eosinophils that appears to be proportional to the severity of the illness. We evaluate the effect of inhaled steroids and of theophylline on sputum eosinophilia and bronchial reactivity and discuss the role of eosinophils on bronchial hyperreactivity. Finally we discuss the use of induced expectoration in clinical practice in asthma. PERSPECTIVES: The analysis of induced sputum could well become a valuable tool in the clinical evaluation and monitoring of asthma in the same way as symptoms and abnormalities of lung function. CONCLUSIONS: Induced expectoration has certainly contributed to the understanding of the cellular and molecular mechanisms of asthma as well as the role of bronchial inflammation in the clinical manifestations of the disease. [less ▲]

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See detailCytokine production from sputum cells after allergenic challenge in IgE-mediated asthma
Bettiol, Jeanne; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(12), 1145-1150

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ... [more ▼]

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ammation. Methods: By applying the technique of induced sputum to collect airways cells, we have assessed the spontaneous production of a set of cytokines, including interleukin-4, 6, 10, interferon-gamma and tumour necrosis factor-alpha 6 h after a bronchial allergenic hallenge with Dermatophagoides pteronyssinus (Dpt) in 12 sensitized asthmatics and compared the results obtained after inhalation of saline as control. A group of eight healthy non-allergic subjects was enrolled to control for any non-specific effect of Dpt. Cytokines were measured by a dynamic immunoassay during a 24-h sputum cell culture. Results: Allergen challenge in sensitized asthmatics caused an acute and a late bronchospasm together with a rise in sputum eosinophil counts. Afterwards allergen sputum cells from allergic asthmatics displayed a rise in their production of IL-4 (P < 0.01), IL-6 (P < 0.05) and IL- 10 (P < 0.05) when compared to saline. By this time sputum generation of IL- 4 in atopic asthmatics was greater than in healthy subjects (P < 0.001). Furthermore, in allergic asthmatics there was a strong correlation between the rise in interleukin-4 production from sputum cells and the rise in sputum eosinophils (r = 0.87, P < 0.001). Conclusions: Sputum cell culture is a useful model to assess cytokine production in allergic asthmatics who show a marked up-regulation of Th2 cytokines following acute allergen exposure. The rise in sputum eosinophil count following allergen challenge strongly correlates with the rise in IL-4 generation from sputum cells. [less ▲]

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See detailMatrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge
Cataldo, Didier ULg; Bettiol, J.; Noël, Agnès ULg et al

in CHEST (2002), 122(5), 1553-1559

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the ... [more ▼]

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the induced sputum recovered from patients during a late-phase reaction. Method: Eight allergic asthma patients and five healthy control subjects inhaled a dose of Dermatophagoides pteronyssinus extract corresponding to the provocative concentration of the allergen causing a 20% fall in FEV1 and saline solution. Lung function was carefully monitored for 6 h, and an induced sputum test was performed at 6 h after sham challenge or allergen challenge. The total and differential cell counts were analyzed, and the levels of MMP-9 (by enzyme-linked immunosorbent assay [ELISA] and zymography), TIMP-1 (by ELISA), and albumin (by rocket immunoelectrophoresis) were measured. Results: The sputum eosinophil counts (p < 0.01) and MMP-9 levels (p < 0.05) increased significantly in atopic asthma patients after undergoing the allergen challenge but did not in the control subjects. By contrast, TIMP-1 and albumin levels were not significantly increased in any group. MMP-9 levels, measured after the allergen challenge in asthmatic patients, were significantly correlated with FEV1 variations after allergen inhalation (r = 0.51; p < 0.05) and with the sputum neutrophil percentage (r = 0.71; p < 0.01). Conclusion: The levels of MMP-9, but not TIMP-1, increase after inhaled allergen challenge in the sputum of allergic asthmatic patients. This protease increase may lead to a transient imbalance between MMP-9 and TIMP-1 favoring proteolytic extracellular matrix degradation. [less ▲]

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See detailLe medicament du mois. L'association budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH)
Louis, Renaud ULg

in Revue Médicale de Liège (2002), 57(11), 741-4

The combination of budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH) in the same dry powder inhaler (turbohaler) results in a drug that possesses powerful bronchial anti-inflammatory ... [more ▼]

The combination of budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH) in the same dry powder inhaler (turbohaler) results in a drug that possesses powerful bronchial anti-inflammatory, bronchoprotective and bronchodilating activities. Symbicort TH is registered as a maintenance treatment for asthma from the age of 12 years. This drug is indicated in the treatment of moderate and severe persistent asthma as well as in asthma which remains mild persistent despite the regular use of low doses of inhaled corticoids alone. Symbicort TH rapidly improves asthma control by reducing symptoms, relief medication consumption and by improving lung function. Importantly, when taken regularly over a prolonged period, the drug reduces the number of mild and severe exacerbations. The dose of Symbicort TH is adjustable according to the disease severity and generally fluctuates between 2 x 1/24 h and 4 x 2/24 h. Symbicort TH is a simple and a efficient treatment likely to improve the compliance of asthmatics to their treatment in real life. [less ▲]

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See detailSputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness
Louis, Renaud ULg; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(10), 907-912

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This ... [more ▼]

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This study aimed to assess the distribution of sputum eosinophil count and its relationship with methacholine bronchial hyperresponsiveness in mild to moderate steroid-naive asthmatic people. METHODS: Sputum was induced by inhalation of hypertonic saline (NaCl 4.5%) in 118 mild to moderate steroid-naive asthmatic people consecutively recruited from our outpatient clinic, and in 44 healthy people. The asthma group was selected on the basis of an forced expiratory volume in 1 s (FEV(1)) of > or = 70% predicted, and a provocative methacholine concentration causing a fall of 20% in FEV(1) (PC20 methacholine; PC(20)M) < or = 16 mg/ml. RESULTS: In the asthma group, the median (range) of the percentage and the absolute values of sputum eosinophils were 4.8% (0-75) and 38 10(3)/g (0-14,191), respectively, vs 0% (0-2.3) (P < 0.001) and 0 10(3)/g (0-53) (P < 0.001) in healthy participants. Based on the 95% percentile for normal values calculated from our healthy group, 69% of the asthma group had significantly raised sputum eosinophil count (that is > 2%). In the asthma group, multiple regression analysis followed by a stepwise procedure revealed that sputum eosinophil count was significantly and inversely associated with PC(20)M accounting for 16% of its total variance (P < 0.001) while neutrophil counts positively related to PC(20)M accounting for 4% of total variance (P < 0.05). By contrast, no significant relationship was found between either eosinophil or neutrophil counts and the slope of forced vital capacity (FVC) vs FEV(1) from the methacholine challenge. CONCLUSIONS: We conclude that two-thirds of people in the mild to moderate asthma group had increased sputum eosinophilia, which plays a limited role in determining the degree of methacholine airway hyperresponsiveness. [less ▲]

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See detailMethods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation
Efthimiadis, A.; Spanevello, A.; Hamid, Q. et al

in European Respiratory Journal (2002), 20(Suppl. 37), 19-23

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See detailClinical applications of assessment of airway inflammation using induced sputum
Pavord, I. D.; Sterk, P. J.; Hargreave, F. E. et al

in European Respiratory Journal (2002), 20(Suppl. 37), 40-43

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See detailMatrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation
Cataldo, Didier ULg; Tournoy, K. G.; Vermaelen, K. et al

in American Journal of Pathology (2002), 161(2), 491-498

We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and ... [more ▼]

We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils; were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. in contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergenexposure. [less ▲]

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See detailEvidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Louis, Renaud ULg; Cataldo, Didier ULg; Buckley, M. G. et al

in European Respiratory Journal (2002), 20(2), 325-331

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in ... [more ▼]

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in severe asthma and sputum eosinophilia in sonic COPD patients. In an attempt to further characterise these two syndromes according to pathology, the current authors have conducted a study of induced sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy individuals. Sputum was analysed for cytology and levels of eosinophil cationic protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule-1. The COPD subjects differed from the asthmatics as they had higher sputum neutrophil and lower columnar epithelial cell counts, but there were no differences in any soluble marker studied. When compared to control subjects, both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels. In a subset of COPD subjects with Sputum eosinophilia (>3% of total cells), significantly increased levels of tryptase were detected. In conclusion, although chronic obstructive pulmonary disease is a more neutrophilic disease than asthma, the two diseases are difficult to distinguish on the basis of sputum levels of the soluble markers traditionally associated with asthma. However, a subset of patients with chronic obstructive pulmonary disease with airway eosinophilia and mast-cell activation might represent a distinct pathological phenotype. [less ▲]

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See detailClinique et cytologie sputaire de l'asthme intrinseque
Bettiol, J.; Radermecker, Maurice ULg; Louis, Renaud ULg

in Revue Médicale de Liège (2002), 57(4), 223-7

The diagnosis of intrinsic asthma is evoked in patients with clinical criteria of asthma but, who contrarily to atopic asthmatics, lack history of allergy, specific IgE and skin positive reaction towards ... [more ▼]

The diagnosis of intrinsic asthma is evoked in patients with clinical criteria of asthma but, who contrarily to atopic asthmatics, lack history of allergy, specific IgE and skin positive reaction towards common aeroallergens of the environment. While the bronchial cytology of these two types of asthma is comparable, the immunological mechanisms of intrinsic asthma remain poorly understood because the factors responsible for the bronchial inflammation are unknown. Intrinsic asthma normally begins in adulthood and carries often a more severe prognosis. This disease is more frequent in women and is often associated to nasal polyposis and/or aspirin hypersensitivity. In this work, we have retrospectively studied the demographic and clinical characteristics, as well as the lung function and the sputum cell counts of intrinsic asthmatic outpatients seen during the period of 1996 to 1998 in the Pneumology Department of the CHU Sart Tilman. [less ▲]

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: possible involvement in allergic inflammation
Bureau, Fabrice ULg; Seumois, G.; Jaspar, F. et al

in Pflügers Archiv : European Journal of Physiology (2002), 443

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation.
Bureau, Fabrice ULg; Seumois, Gregory; Jaspar, Fabrice et al

in Journal of Allergy and Clinical Immunology (The) (2002), 110(3), 443-9

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by ... [more ▼]

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by inducing the expression of antiapoptotic proteins. Three members of the inhibitor of apoptosis protein (IAP) family, namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated. METHODS: Blood and sputum were obtained from healthy subjects and atopic asthmatic patients. Blood eosinophils were isolated by means of magnetic selection. Expression of CD40, IAPs, and Bcl-2 proteins was investigated by using flow cytometry, immunoblotting, or both. CD40 stimulation was achieved with agonistic antibodies or soluble ligands. Apoptosis was assessed by staining with propidium iodide and FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense oligonucleotides. RESULTS: Freshly isolated eosinophils from healthy and asthmatic patients did not express CD40. Conversely, eosinophils expressed CD40 spontaneously when cultured for 48 hours. At this time point, CD40 stimulation significantly delayed eosinophil apoptosis. Inhibition of eosinophil apoptosis was accompanied by induction of c-IAP2 but not c-IAP1, XIAP, Bcl-x(L), or Bfl-1/A1 expression. Antisense knockdown of c-iap2 abolished CD40-induced enhancement of eosinophil survival. Sputum cells from asthmatic patients, unlike those from healthy subjects, substantially expressed CD40 and c-IAP2. Moreover, a strong correlation was found between the percentage of eosinophils in the sputum from asthmatic patients and the sputum level of CD40 and c-IAP2 expression. CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil survival through induction of c-IAP2 expression and suggest a role for this mechanism in allergic inflammation. [less ▲]

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See detailInduced sputum - Comparison between isotonic and hypertonic saline solution inhalation in patients with asthma
Cataldo, Didier ULg; Foidart, Jean-Michel ULg; Lau, L. et al

in CHEST (2001), 120(6), 1815-1821

Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect ... [more ▼]

Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor. Study objectives: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation. Patients: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion. Methods: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled For three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography. Results: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05). Conclusion: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins. [less ▲]

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