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P Gosset

Publications and source records attributed to P Gosset.

At least 73 records · Page 4Linked to original sources
PubMed1998

Transforming growth factor-beta1 in sarcoidosis.

Transforming growth factor-beta (TGF-beta) is a cytokine that promotes extracellular matrix accumulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, granuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-beta1 was evaluated in bronchoalveolar lavage (BAL) fluid and culture supernatants of alveolar macrophages (AM) from 73 patients with biopsy-proven sarcoidosis. Disease activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) and/or demonstrated increasing opacities on chest radiography. Pulmonary function tests were performed in all patients including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon monoxide (DL,CO). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. Immunohistochemistry was used to evaluate the cell distribution of TGF-beta1 on lung specimens. TGF-beta1 levels in BAL and in AM supernatants were not different between sarcoidosis and healthy subjects, whereas they were markedly increased in IPF. However, the TGF-beta1 level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-beta1 level in BAL was increased in active sarcoidosis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-beta1 levels in BAL correlated significantly with the lymphocyte percentage. TGF-beta1 staining assessed by immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bronchiolar epithelial cells, in hyperplastic type II pneumocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-beta1 is associated with functional impairment in patients with pulmonary sarcoidosis.

Adult↗
PubMed1997

A new inward rectifier potassium channel gene (KCNJ15) localized on chromosome 21 in the Down syndrome chromosome region 1 (DCR1).

The Down syndrome chromosome region-1 (DCR1) on subband q22.2 of chromosome 21 is thought to contain genes contributing to many features of the trisomy 21 phenotype, including dysmorphic features, hypotonia, and psychomotor delay. Isolation, mapping, and sequencing of trapped exons and captured cDNAs from cosmids of this region have revealed the presence of a gene (KCNJ15) encoding a potassium (K+) channel belonging to the family of inward rectifier K+ (Kir) channels. The amino acid sequence deduced from the 1125-bp open reading frame indicates that this gene is a member of the Kir4 subfamily; it has been named Kir4.2. It is expressed in kidney and lung during human development and in several adult tissues including kidney and brain. After Kir3.2 (GIRK2), Kir4.2 is the second K+ channel gene of this type described within the DCR1.

Adult↗
PubMed1997

POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.

POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as treatments which act through an anti-cytokine mechanism.

Adult↗
PubMed1997

MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis.

Exposure to coal dust leads to the development of coal worker's pneumoconiosis (CWP), a disease associated with an accumulation of macrophages in the lower respiratory tract. Mechanisms controlling monocyte recruitment are still poorly understood. Since monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic factor for blood monocytes, we analysed the presence of MCP-1 in the pulmonary compartment of patients with CWP. Bronchoalveolar lavage fluid (BALF) from 16 nonsmoking control subjects and 27 nonsmoking CWP patients (16 with simple pneumoconiosis (SP) and 11 with progressive massive fibrosis (PMF)) was analysed. Alveolar macrophages (AMs) were purified by adherence and BALF was concentrated tenfold by lyophilization. MCP-1 was measured in BALF and in 3 h AM supernatants using a sandwich enzyme-linked immunosorbent assay (ELISA). The localization of MCP-1 in lung tissue was determined by immunohistochemistry on tissue sections from three patients with CWP and two control subjects. MCP-1 levels were significantly higher in concentrated BALF from patients with SP or PMF (median 370 and 555 pg x mL-1, respectively) than in those from control subjects (median 11 pg x mL-1) (p<0.001). Released MCP-1 in AM supernatants was enhanced in patients with CWP (median 83 pg x mL-1) but compared to controls (median 41 pg x mL-1) this level did not reach significance. Although significantly increased, AM counts in BALF from patients with CWP did not correlate with MCP-1 levels. MCP-1 levels in BALF correlated with MCP-1 levels in AM supernatants (p=0.47; p<0.02). In control lung specimens, MCP-1 was expressed by a few AMs, type II pneumocytes and perivascular smooth muscle cells. CWP sections were characterized by an increased number of AMs and mainly by the presence of fibroblasts (in the myogenic area of fibrotic lesions) and hyperplastic type II pneumocytes, which were strongly immunostained for MCP-1. Our data demonstrate that: 1) patients with coal worker's pneumoconiosis have a marked pulmonary overproduction of monocyte chemoattractant protein-1; and 2) in addition to alveolar macrophages, fibroblasts (probably myofibroblasts) and hyperplastic type II pneumocytes may also be responsible for this increased level of monocyte chemoattractant protein-1 in coal worker's pneumoconiosis.

Aged↗
PubMed1997

Interleukin-8 secretion in patients with allergic rhinitis after an allergen challenge: interleukin-8 is not the main chemotactic factor present in nasal lavages.

BACKGROUND: Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and primed eosinophils. In allergic rhinitis, allergen exposure triggers leucocyte recruitment. OBJECTIVE: We evaluated in this study IL-8 secretion and the neutrophil chemotactic activity in nasal lavages collected after a nasal allergen challenge. Moreover, the participation of IL-8 in the neutrophil chemotactic activity was quantified. METHODS: Four healthy subjects and 19 patients with allergic rhinitis were exposed to a nasal allergen challenge. As a control, saline challenge was performed in four patients with allergic rhinitis. Concentration of IL-8 was measured by ELISA in nasal lavages collected before and after challenge. Neutrophil chemotactic assay was developed using a 48-well chemotaxis microassembly. RESULTS: After allergen challenge, the healthy subjects, the four patients receiving saline and one patient exposed to allergen did not respond; seven patients presented a single early reaction and 11 patients a dual response. For healthy subjects and the four patients exposed to saline, the level of IL-8 did not increase after challenge in comparison with that at baseline. After allergen challenge, two peaks of IL-8 release were observed for patients with allergic rhinitis during the early (30 min to 1 h 30 min) and the late periods (3 h 30 min to 9 h 30 min), however the difference was not significant for the early period. During the late period, a significant increase in IL-8 concentrations was detected for the patients developing a dual response, whereas the difference was not significant for those presenting only an early reaction. The neutrophil chemotactic activity of nasal lavages from patients with allergic rhinitis collected during the early and the late reactions (17 +/- 2.1 and 23.3 +/- 2.8 neutrophils per high power field (hpf), respectively) was significantly higher than the activity of lavage fluid collected at baseline (9.2 +/- 1.8 neutrophils per hpf). Nevertheless, the addition of a neutralizing anti-IL-8 antibody inhibited weakly the chemotactic activity of lavage fluid from rhinitic patients collected during the early or the late periods (18 and 11% of inhibition) (P = NS). CONCLUSION: These data show that allergen challenge increased significantly the secretion of IL-8 for the patients with allergic rhinitis. However, neutralization of IL-8 in nasal lavages by a specific antibody revealed that the role of this chemokine in granulocyte infiltrate was limited, suggesting that IL-8 acts in connection with other chemotactic factors in this recruitment.

Adult↗
PubMed1997

Altered compartmentalization of transforming growth factor-beta in asthmatic airways.

BACKGROUND: Asthma is characterized by alterations of the bronchial epithelium associated with inflammatory cell infiltrates and sub-epithelial fibrosis. Transforming Growth Factor-beta (TGF-beta) is an anti-inflammatory and fibrosing cytokine normally present in bronchial epithelial cells and also potentially produced by inflammatory cells. Thus, TGF-beta could play a role in the asthmatic process, and its expression could be modified in asthmatic airways. OBJECTIVE: To test this latter hypothesis, we studied the bronchial distribution of TGF-beta in asthmatic patients. METHODS: TGF-beta 1, 2, 3 distribution was studied by immunohistochemistry in bronchial biopsies from 12 asthmatic patients and 10 non-asthmatic subjects. RESULTS: Bronchial epithelial cells from asthmatics were negative or faintly positive while a bright staining was detected in these from non-asthmatics (P < 0.01). In both groups, when inflammatory cells were present beneath the basement membrane, they were stained by the anti-TGF-beta antibody. CONCLUSION: This study shows an altered compartimentalization of TGF-beta in asthma. (a) TGF-beta is scarse in asthmatic bronchial epithelial cells, which could favour the perennization of the bronchial inflammation, and (b) TGF-beta is present in inflammatory cells beneath the basement membrane, where it could be involved in the frequent sub-epithelial fibrosis.

Adult↗
PubMed1997

Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells.

BACKGROUND: The allergic inflammatory reaction is characterized by leucocyte adherence and infiltration processes which are controlled by the expression of adhesion molecules on the surface of vascular endothelium. One of the main mediators implicated in allergic reactions is represented by histamine. Histamine is a potent activator of endothelial cells (EC): it induces the expression of P-selectin on the surface of endothelium and the secretion of IL-6 and IL-8. OBJECTIVES: Loratadine (L), a histamine H1-antagonist, and one of its active metabolites, descarboxyethoxyloratadine (DCL), were studied at different concentrations for their ability to reduce the histamine-induced activation of human umbilical vein EC (HUVEC). METHODS: HUVEC were stimulated in the presence of histamine at 10(-6) M, 10(-5) M and 10(-4) M. We assessed by ELISA the expression of P-selectin on EC surface, as well as cytokine production in EC supernatants of 24 h culture. RESULTS: Our results showed that for a 10(-4) M-histamine stimulation, L and DCL have a similar inhibitory effect on P-selectin expression (IC50 = 13 x 10[-9] M and 23 x 10[-9] M, respectively). L and DCL inhibited significantly IL-6 and IL-8 secretion induced by histamine with a more powerful efficiency of the active metabolite. For the dose of 10(-4) M histamine, a 50% inhibition of IL-6 secretion was obtained for a dose of DCL equal to 2.6 x 10(-12) M whereas the same magnitude of effects were only reached for a higher concentration of L (0.3 x 10[-6] M). Similar results were obtained for IL-8 (IC50 = 0.2 x 10[-6] M for L and 10[-9] M for DCL). Analysis of IL-8 mRNA expression by RT-PCR was in accordance with these data. CONCLUSION: These results demonstrate that both L and DCL are active to reduce the histamine-induced activation of EC. Interestingly, DCL seems to be effective at lesser concentrations especially to inhibit cytokine secretion.

Cells, Cultured↗
PubMed1996

Interactions between endothelial cells and effector cells in allergic inflammation.

The local inflammatory response that occurs after repeated exposure to allergens or during the late-phase reaction results from a complex network of interactions between inflammatory cells (mast cells, eosinophils, macrophages) and resident cells belonging to the lung structure itself like EC, fibroblasts, or bronchial epithelial cells. Among structural cells, EC represent critical elements: they control leukocyte traffic through the expression of adhesion molecules; they are also able to amplify leukocyte activation through the production of proinflammatory cytokines like IL-1, IL-6, or of chemokines like IL-8. Three cell models have been successively considered. When supernatants of alveolar macrophages, recovered from patients exhibiting a late asthmatic response after allergen exposure, were tested on HUVEC cultures, a TNF alpha-dependent ICAM-1 and E-selectin overexpression was observed. Among mast-cell mediators, histamine was already known to induce a rapid and transient expression of P-selectin; we demonstrated that histamine also induced an IL-6 and IL-8 secretion by HUVEC, which was concentration-dependent and inhibited by H1 or H2 receptor antagonists. Finally purified eosinophils obtained from donors with hypereosinophilia similarly increased adhesion molecule expression and chemokine production. The precise nature of the eosinophil product(s) involved in this process is currently under investigation.

Asthma↗
PubMed1996

In vitro assessment of environmental toxicology using alveolar cells as target.

Biphasic culture of alveolar cells (alveolar macrophages and type II cells) has been widely developed and permits a precise evaluation of the toxic effects of air pollutants. Clearly, in vitro exposure of alveolar cells to high concentrations of oxidant gases is responsible for a loss of cell viability. In contrast, when exposed to realistic concentrations of gases (NO2, O3), cell viability is not altered and various proinflammatory mediators are released. This in vitro model has proved to be sensitive at levels of gas exposure of ambient air quality standards and appears a sensitive biological indicator of air pollutant cell toxicity.

Air Pollutants↗
PubMed1996

Expression of leucocyte-endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-alpha).

Coal workers' pneumoconiosis (CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in alveolar spaces. In this study, we investigated in CWP the implication of adhesion molecules such as E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) and the role of TNF-alpha which is one of the cytokines inducing their expression. Adhesion molecule expression was analysed by immunohistochemistry on lung biopsies from patients with CWP and from healthy subjects. In parallel, soluble adhesion molecules were detected in bronchoalveolar lavage fluids (BALF) from patients by specific ELISA. The involvement of TNF in the induction of these adhesion molecules was measured (i) by immunohistochemistry on sections from lung fragments, and (ii) by evaluating in vitro the expression of adhesion molecules on endothelial cells and on alveolar epithelial cells in the presence of alveolar macrophage supernatants. In control subjects, a weak staining of ICAM-1 was detected only in alveolar walls, while E-selectin and VCAM-1 were undetectable. In pneumoconiotic patients, ICAM-1 was expressed at a high level by endothelium, by alveolar and bronchial epithelial cells and by alveolar macrophages. E-selectin and VCAM-1 expression remained undetectable. Measurement of soluble adhesion molecule showed that only the concentration of sICAM-1 was significantly increased in BALF from patients with CWP compared with controls. The involvement of TNF in this ICAM-1 expression was shown by the in vitro effect of alveolar macrophage supernatants on adhesion molecule expression by endothelial cells and epithelial cells (this effect was neutralized by anti-TNF antibodies) and by the increased production of TNF in the lung of pneumoconiotic patients. These data provide evidence for the involvement of ICAM-1, induced at least in part by alveolar macrophage-derived TNF, in the development of the inflammatory reaction in CWP.

Aged↗
PubMed1996

[Effects of ambulatory respiratory rehabilitation on exercise tolerance and quality of life in chronic obstructive lung disease patients].

Respiratory rehabilitation is a multidisciplinary medical approach which allows a total care of patients suffering from COPD. Optimisation of bronchodilator treatment, health education, cessation of smoking, dietetic, relaxation and re-entrainment to effort. We report out experience concerning 88 BPCO (mean age 62.1, FEV1 of 1.4 litres; or 48% of predicted normal); these 88 patients were cared for on an ambulatory basis at our centre for two hours per session, three times per week for seven weeks. The objective results were analysed on exercise tests before and after treatment. For ventilation, there was a significant improvement in the power developed (from 45.5+/-17.1 to 53.4+/-23 watts; p<0.001) without any change in the oxygen consumption (VO2), ventilation (VE) or heart rate (FC) and of oxygen pulse (VO2/FC). For the same level of power (80% of maximum power for the initial exercise test) there was a significant lowering of ventilation (V=33.5+/-9.4 to 30.7+/-7.4 litres per minute, p<0.001), cardiac frequency (FC: from 116.9+/-16 to 111.1+/-13.1 beats per minute, p<0.001) as well as the oxygen pulse (VO2/FC: from 7.9+/-2.7 to 8.3+/-3.7). At the maximum on the exercise test all the parameters studied were significantly better: watts, VO2, VE, cardiac frequency and VO2/FC. A study of the visual analogue scale (EVA), analysing sleep, anxiety, dyspnoea and the physical aspects showed a significant improvement in the four subjective parameters. Respiratory rehabilitation of BPCO practiced as an out patient has shown an improvement in exercise tolerance in every day activities and improvement in dyspnoea and in the quality of life.

Aged↗
PubMed1996

Toxicity of ferric oxide and benzo[a]pyrene alone or in combination in respiratory tract of Sprague Dawley rats.

The association of small quantities of ferric oxide with Benzo[a]Pyrene (BaP) appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic BaP metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe2O3 (3 mg) or BaP (3 mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated) were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each BAL we have obtained protein measurement, cells were stained with May-Grünwald-Giemsa method and slides were studied with polarised light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard. After a quantitative Dot-Blot of the samples of BAL, an immunodetection of alpha(1)-antitrypsin (alpha(1)AT) was performed. The inhibitory capacity of alpha(1)AT was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased MDA level for rats intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)AT was decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The inhibitory capacity of alpha(1)AT was lower in groups of rats instilled with toxics.

Animals↗
PubMed1996

Toxicity of iron oxides and metabolites of benzo[a]pyrene alone or in combination in cells culture and identification by laser microprobe mass spectrometry.

The goal of the gas-phase studies of well-characterized transition-metal systems is to enhance our understanding of the chemistry and sometimes of the toxic, carcinogenic effects of transition metal oxide clusters and compounds. The analysis of inorganic solids by time of flight laser microprobe mass spectrometry (TOF-LMMS) shows the formation of clusters in the mass spectra which can be used for the identification of inorganic particles. First, we have applied non-resonance ionization (delta = 226 nm) or resonant ionization (delta = 293.7 nm) of iron to study the non stoichiometric Fe1-xO, Fe3O4, Fe2O3 compounds in positive mode by TOF-LMMS. The positive mass spectra are characterized by many differences between the clusters detected and their intensities. Then, we have analysed the benzo[a]pyrene (BaP), the 1-hydroxbenzo[a]pyrene (1-OH-BaP) and the 3-hydroxybenzo[a]pyrene (3-OH-BaP) of TOF-LMMS and by Fourier Transform Irons Cyclotron Resonance Mass Spectrometry (FT-ICR-MS). It is possible to distinguish these different compounds by their respective fingerprint. Later on, we have studied toxic effects of iron oxides (Hematite Fe2O3 and Magnetite Fe3O4), benzo[a]pyrene (BaP) and Pyrene, alone or in combination. The LC50 was appreciated by colony-forming cell culture method. Cells were observed by electron microscopy and the valence of particles was analysed by TOF-LMMS. With Fe2O3 we have observed a significant decrease (20%) at higher concentration (0.5 mmol/l) and smaller quantities of BaP were highly toxic. The association of BaP at the LC10 dose (0.05 mumol/l) with growing doses of Fe2O3 or Fe3O4 (0.0125; 0.025; 0.05; 0.1; 0.2 mmol/l), appeared to increase the toxic effect of BaP 3 to 4 times. These results suggest that Fe2O3 and Fe3O4 alone are not very toxic but the association of one of these compounds with BaP increases the toxicity of the latter. On the other hand, TOF-LMMS seems to show a metabolization of iron oxide into reduced form. But, it is necessary to raise the ambiguity about the iron which is always in the cells present. For that purpose, studies with iron oxides enriched by 54Fe isotope have begun.

Benzo(a)pyrene↗
PubMed1995

Impaired secretion and mRNA expression of monokines by alveolar macrophages from nonsmoking patients with alcoholic liver cirrhosis.

Alveolar macrophages (AM) exposed to microorganisms secrete cytokines that are important to lung defense. Since alcoholic liver cirrhosis (ALC) patients are susceptible to lung infections, the ability of AM in such patients to produce the cytokines tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 was evaluated by mRNA expression and protein secretion. Adherent AM from ALC and alcoholic patients and controls were cultured with and without lipopolysaccharide (LPS): Mean cytokine levels in ALC and alcoholic subjects were not significantly different than in controls. However, LPS-stimulated AM from 13 of 29 ALC patients exhibited a reduced ability, compared with that from controls, to secrete the cytokines (P < .05 for all 3). Specific mRNA expression was also impaired in the 13 patients, and their liver diseases were more severe than those of other patients. Impaired cytokine production by AM in ALC patients with severe cirrhosis may account for their increased susceptibility to lung infections.

Adult↗
PubMed1995

Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells.

Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site.

Adult↗
PubMed1995

Expression of E-selectin, ICAM-1 and VCAM-1 on bronchial biopsies from allergic and non-allergic asthmatic patients.

The bronchial mucosa of asthmatic patients is characterized by a large influx of eosinophils, monocytes and lymphocytes. Leucocyte migration and accumulation is thought to involve adhesion molecules, as shown in an animal of allergic asthma and in humans with other allergic diseases. The aim of this study was to evaluate the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) on endothelium and epithelium in bronchial biopsies obtained from patients with allergic (n = 17) and non-allergic asthma (n = 18). Bronchial biopsies were taken in asthmatic patients and control subjects (n = 10) by fiberoptic bronchoscopy and embedded in paraffin. The cellular infiltrate was evaluated by May-Grünwald-Giemsa staining. Adhesion molecule expression was analyzed by immunohistochemistry using mouse monoclonal antibodies; the results were expressed as the percentage of positive cells. For each patient, we evaluated the severity of asthma as defined by the AAS score and the treatment. In controls, low expression of ICAM-1 was observed on the epithelium and endothelium (9.6 +/- 2.7 and 11.2 +/- 4.1%, respectively), while E-selectin and VCAM-1 were not expressed. In patients with allergic asthma, a significant increase of ICAM-1 expression was observed on epithelium and endothelium (28 +/- 5.3 and 35.6 +/- 5%, respectively), whereas E-selectin (17.4 +/- 4.8%) and VCAM-1 (12.8 +/- 3.6%) were overexpressed only on endothelium. In allergic asthmatic patients, adhesion molecule expression on endothelium was correlated with eosinophil and total leucocyte infiltrate (p < 0.05). In contrast, adhesion molecule expression in biopsies from patients with non-allergic asthma (14.1 +/- 5.2 and 15.3 +/- 3.6% for ICAM-1 expression on epithelium and endothelium, respectively) was not significantly different from the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗