0000000000034471
AUTHOR
Ferlinz R
Sezernierter Interleukin-2-Rezeptor als Aktivitätsparameter der Sarkoidose*
Serum sIL-2-R levels were measured in 28 sarcoidosis patients at multiple time points before, during, and after therapy, with a mean follow-up time of 10.2 +/- 5.2 months, and the results compared with the clinical activity of the disease. Before therapy, 20 out of 24 episodes with active disease exhibited elevated levels of sIL-2-R (918 +/- 362 U/ml). In inactive disease after tapering off corticoid therapy the sIL-2-R levels were 453 +/- 274 U/ml. Disease activity under therapy also correlated with sIL-2-R serum levels. 23 out of 29 episodes with signs of activity under therapy had elevated sIL-2-R levels (808 +/- 409 U/ml). Only three of 28 patients in whom disease activity ceased after …
Das chemotaktische Verhalten von Alveolarmakrophagen und Blutmonozyten nach Expositionen mit unterschiedlichen NO2-Konzentrationen
The chemotaxis of alveolar macrophages (AM) and blood monocytes (BM) is important in the elimination of particles and microorganisms which have invaded the lung. The effect of nitrogen dioxide (NO2) on chemotaxis was tested on AM obtained by diagnostic bronchoscopy from five patients suspected of having bronchial carcinoma (four men, one woman; mean age 59 +/- 10 years). Blood monocytes were also studied with blood from seven healthy subjects (five men, two women; mean age 32 +/- 10 years). These cells were placed on polycarbonate membranes for 15 min each, exposed to NO2 concentrations between 1.0 and 5.0 parts per million (ppm), and then incubated with complement component C5a as chemotac…
Interleukin-2 receptor gene expression by bronchoalveolar lavage lymphocytes in pulmonary sarcoidosis.
Current concepts of the immunopathogenesis of sarcoidosis favor a central role of activated, interleukin-2 (IL-2) producing helper T-cells at sites of inflammation. Normally, activated T-cells release IL-2 and express IL-2 receptors (IL-2R). IL-2R+ cells, however, are not uniformly found in patients with clinically active disease. To determine whether the lack of IL-2R+ cells is caused by a dysregulation of the IL-2R gene or by the mode of T-cell activation in pulmonary sarcoidosis, we quantified IL-2 and IL-2R m-RNA transcripts, IL-2 release, and IL-2R surface protein in peripheral blood lymphocytes of patients with sarcoidosis and normal control subjects before and after in vitro stimulat…
An experimental model for the exposure of human ciliated cells to sulfur dioxide at different concentrations
Mucociliary transport is an important nonimmunological defense mechanism of the respiratory tract. The aim of this study was to investigate the effect of sulfur dioxide (SO2) at different concentrations on ciliary beat frequency (CBF). Ciliated cells were obtained from 12 volunteers by nose brush. CBF was quantified using video-interference microscopy. The cells were placed on a polycarbonate membrane in contact with the surface of a reservoir filled with RPMI 1640 (bicarbonate buffered) or Ringer's (electrolyte) solution, allowing the cells to be supplied by capillarity. In an exposure chamber the cells were exposed for 30 min to SO2 2.5-12.5 ppm at 37 degrees C and 100% air humidity. SO2 …
In vitro study of human alveolar macrophage and peripheral blood mononuclear cell reactive oxygen-intermediates release induced by sulfur dioxide at different concentrations
Sulfur dioxide (SO2) is a major air pollutant in urban areas. Alveolar macrophages (AM) located on the alveolar surface are in direct contact with this inhaled gas. We evaluated the dose-dependent effect of SO2 exposure on the oxidative metabolism of AM and peripheral blood mononuclear cells (PBMNC) by measuring the spontaneous and stimulated reactive oxygen intermediates (ROI) release. AM or PBMNC were placed on a polycarbonate membrane, which was in direct contact with the surface of a nutrient reservoir. For exposure of the cells to SO2 a special chamber was employed, in which humidified standard air with 5% CO2 at 37 degrees C was mixed with SO2 at the desired concentration. Periods of …
Nitrogen Dioxide-induced Reactive Oxygen Intermediates Production by Human Alveolar Macrophages and Peripheral Blood Mononuclear Cells
Alveolar macrophages located on the alveolar surface have contact with air pollutants. We evaluated the dose-dependent effect of nitrogen dioxide exposure on the oxidative metabolism of alveolar macrophages and peripheral blood mononuclear cells by measuring the spontaneous and stimulated reactive oxygen intermediates production. Alveolar macrophages or peripheral blood mononuclear cells were placed on a polycarbonate membrane, which was in direct contact with the surface of a nutrient reservoir. The cells were exposed to nitrogen dioxide during different periods of time, varying between 30 and 120 min at concentrations ranging from 0.1 to 0.5 ppm. Exposure of alveolar macrophages to nitrog…
Modulation of IL-1?, IL-6, IL-8, TNF-?, and TGF-? secretions by alveolar macrophages under NO2 exposure
Activated alveolar macrophages (AMs) secrete interleukine (IL)1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β), whose inflammatory and fibroblast-activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO2 in concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37°C. AMs were fixed on a polycarbonate membrane and placed on culture medium. A culture was established, with the exposed AM (nonstimulated or stimulated with 1 μg/ml lipopolysaccharide [LPS]), and the remaining cells were used to determine the cy…
Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage.
Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms and is associated with a poor local cellular immune response. 16 patients with non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to investigate the lymphocyte surface antigens utilizing the immunoperoxidase technique. Analysis of blood lymphocytes was performed in parallel. 8 patients with previous sarcoidosis in complete remission who underwent BAL and 10 normal blood donors served as controls. Among blood lymphocytes the CD3+, CD4+ and CD16+ cell populations were elevated significantly and the T4/T8 ratio was elevate…
Effect of sulfur dioxide on cytokine production of human alveolar macrophages in vitro.
Tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and transforming growth factor-beta are cytokines synthesized by alveolar macrophages. We investigated the effect of sulfur dioxide, a major air pollutant, on the production of these cytokines by alveolar macrophages. The cells were layered on a polycarbonate membrane and exposed for 30 min to 0.0, 1.0, 2.5, and 5.0 ppm sulfur dioxide at 37 degrees C and 100% air humidity. The cells were incubated for 24 h after exposure, thus allowing cytokine release. Cytotoxic effects of sulfur dioxide were evaluated by trypan blue exclusion. Cytokines were measured with enzyme-linked immunosorbent assays (i.e., tumor necrosis factor-alpha, i…
Effect of sulfur dioxide on mucociliary activity and ciliary beat frequency in guinea pig trachea
The effects of 30 min exposure to sulfur dioxide on mucociliary activity (MCA) and ciliary beat frequency (CBF) were studied in 31 guinea pig tracheas. MCA was measured by recording the light reflected from ciliated mucous membranes using an infrared bar code reader. CBF of single ciliated cells obtained by brushing was measured with phase-contrast microscopy. Each tracheal sample was exposed to SO2 at concentrations ranging from 2.5 to 12.5 ppm, or to air for control purposes. MCA and CBF were measured before and immediately after gas exposure. A reduction in mean MCA of 63% (P = 0.0007) and statistically insignificant changes in CBF (P > 0.05) were recorded at concentrations of 2.5 PPM SO…
A macrophage-suppressing 40-kD protein in a case of pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown etiology. Macrophage dysfunctions are claimed to be involved in the pathogenesis. We investigated phagocytosis and oxidative metabolism of alveolar macrophages in a case of pulmonary alveolar proteinosis. These cells phagocytize normally and phagocytizable stimulants cause a normal oxidative burst. In response to the membrane signals phorbolmyristate acetate and aggregated immunoglobulin, however, no stimulated turnover of the oxidative metabolism can be observed. A 40-kD protein found in the lavage fluid mediates this macrophage-inhibiting effect. This phenomenon may contribute to the frequent opportunistic infections seen i…
Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis.
An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of …
Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance.
In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes — erbB2, Ki-ras, and c-myc — in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung t…
Spontaneous Monokine Release by Alveolar Macrophages in Chronic Sarcoidosis
In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration > 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 …
Chemotactic response of human alveolar macrophages and blood monocytes elicited by exposure to sulfur dioxide.
An experimental study was undertaken to investigate the in vitro effect of sulfur dioxide on the chemotactic activity of alveolar macrophages (AM) and blood monocytes (BM). The cells were placed on a polycarbonate membrane and exposed to SO2 0.5, 1.5 and 2.5 ppm for 15 min. Control experiments were performed with exposure of the cells to synthetic air with 5% CO2. After gas exposure the cells were incubated with the chemotactic active agent C5a in 5% carbon dioxide (CO2) at 37 degrees C for 60 min. The numbers of AM and BM passing actively through the membrane were quantified using light microscopy. Our results show a dose-dependent reduction in the migration rate of cells under SO2 exposur…
Correlation of Clinical and Immunologic Parameters of the Inflammatory Activity of Pulmonary Sarcoidosis
The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of…
Oxygen Radical Production by Alveolar Inflammatory Cells in Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease characterized by the accumulation of alveolar macrophages (AMs) and neutrophils in the lower respiratory tract, parenchymal cell injury, and fibrosis of the alveolar structure. Reactive oxygen intermediates (ROI) are claimed to be a major cause of tissue damage in IPF; however, the source of ROI has not been unequivocally identified. AMs, as well as neutrophils, are capable of releasing these agents. The contributions of these possible sources are not known. To address this question, we evaluated the spontaneous and stimulated (PMA or zymosan) ROI release of total bronchoalveolar cells and isolated AMs i…