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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Although alveolar macrophages (AM) are poor accessory cells, alveolar macrophages of patients with sarcoidosis or tuberculosis show an elevated accessory function indicating that the accessory function (AF) of AM can be upregulated.¶Materials and Methods: We examined whether the AF of AM and peripheral blood monocytes (PBM) can be increased by interferon-γ (IFNγ) and whether immunomodulating drugs like cyclosporine A, cyclophosphamide, dexamethasone, and ambroxol are able to modulate the accessory function and the expression of accessory molecules.¶Results: IFNγ increased the AF of AM and PBM up to 309 ± 122% and 152 ± 25%, respectively (p〈0.02, unstimulated control=100%, in all cases). In alveolar macrophages this increase is most efficiently prevented by cyclosporine A (31 ± 13%), followed by cyclophosphamide (64 ± 20%) and dexamethasone (66 ± 20%). In monocytes the IFNg-induced increase in accessory function is prevented only by cyclosporine A (17 ± 7%) and dexamethasone (59 ± 9%). Cyclosporine A was also the most effective drug down-regulating the expression of accessory molecules (CD54, CD58, CD80 and CD86). ¶Conclusions: In summary, the accessory function of alveolar macrophages and monocytes is upregulated by IFNγ and can be controled by immunomodulating drugs.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 65 (1987), S. 893-897 
    ISSN: 1432-1440
    Keywords: Pulmonary alveolar proteinosis ; Alveolar macrophages ; Oxidative metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 in PAP patients. It can be concluded from our data that the high frequency of infections with opportunistic species in these patients can be reduced by therapeutic bronchoalveolar lavage. By this procedure the abnormal macrophage-suppressing protein can be washed out of the lung at an early stage of the disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Air pollution ; Sulfur dioxide ; Ciliary beat frequency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 (S02) 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°C and 100% air humidity. SO2 induced a dose-dependent decrease in CBF of the cells cultured in Ringer's solution. SO2 at 2.5 ppm caused a 42.8 % decrease and at 12.5 ppm a 96.5% decrease (8.1 ± 0.24 versus 0.28 ± 0.20 Hz). CBF of cells cultured in RPMI 1640 was reduced only moderately after 12.5 ppm SO2 exposure (7.9 ± 0.26 versus 6.70 ± 0.30 Hz). In Ringer's solution a decrease in pH was observed after 30 min of S02 exposure to 12.5 ppm to a minimum value of 3.6. By contrast, the pH of RPMI 1640 remained constant at 7.5 under identical conditions. After adding RPMI 1640 to Ringer's solution, CBF increased in parallel to the pH to control values (5.0 ppm: 4.64 ± 0.45 to 8.51 ± 0.60 Hz). These data suggest that the highly water-soluble SO2 reversibly eliminates CBF in correlation with a decrease in pH.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Key words Alveolar macrophages ; Accessory function ; IL-2 ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accessory function allows antigen-presenting cells to produce sufficient secondary signals for optimum T cell proliferation and interleukin-2 (IL-2) production. Alveolar macrophages are inferior accessory cells compared to monocytes (PBM). We report here that the accessory index (AI) of alveolar macrophages and PBM of patients with lung metastases of solid tumors treated with inhalations of human natural IL-2 (hnIL-2) increased following its administration (P〈0.005). The accessory index was significantly elevated from baseline values after 2 weeks of inhalation of 300 000 IU hnIL-2/day (8.2±10.2 compared to 1.1±1; P〈0.001). The inhalation of 150 000 IU also induced increases in the index (AI = 2.3±1.9), however, without reaching statistical significance. In addition at 300 000 IU IL-2/day a significant increase in the accessory index was observed for PBM (4±2.5; P〈0.05). The indices of PBM and alveolar macrophages prior to inhalation showed a significant negative correlation with the age of the patients (r s =  – 0.5; r s =  – 0.8, respectively; P〈0.03 for all comparisons). Our data demonstrate that the inhalational application of hnIL-2 enhances the accessory function of alveolar macrophages and, to lesser extent, the accessory index of PBM, indicating the occurrence of pharmacological immunostimulation.
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  • 5
    ISSN: 1432-1289
    Keywords: Schlüsselwörter Sarkoidose ; Vaskulitiden ; Kollagenosen ; Fibrosierende Alveolitis ; Immunsuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zum Thema Die Sarkoidose und die fibrosierende Alveolitis stellen die klassichen interstitiellen Lungenerkrankungen unbekannter Ätiologie dar, die in der Regel auf eine immunsuppressive Therapie ansprechen. Weniger bekannt ist, daß die pulmonalen Manifestationen von Vaskulitiden und Kollagenosen die Symptomatik dominieren oder gar den systemischen Veränderungen vorauseilen können. Bei den genannten Erkrankungen sind die unterschiedlichen inflammatorischen Prozesse im Bereich des Lungenparenchyms Gegenstand intensiver klinisch-immunologischer Forschung, die soweit vorangeschritten ist, daß differential-therapeutische Überlegungen auf ihrer Basis angestellt werden können. Insbesondere lassen sich mittlerweile durch die Kombination von atemphysiologischen und klinisch-immunologischen Methoden Interventionspunkte für unterschiedliche Therapiemodalitäten definieren. In der folgenden Übersicht wird zunächst auf die Pathogenese, den Verlauf und die Therapieindikationen der einzelnen Krankheitsbilder eingegangen, sodann werden detaillierte Therapievorschläge gemacht. Unter pragmatischen Gesichtspunkten werden Therapieschemata aufgezeigt und differentialtherapeutische Erwägungen dargelegt.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1440
    Keywords: Lung cancer ; Cellular immunity ; Bronchoalveolar lavage fluid ; T-lymphocytes ; Surface antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 elevated in NSCLC patients, but only CD16+ were augmented in SCLC. Cell populations expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2) receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC was associated with antigen distributions similar to controls. No differences between the cohorts were seen in the expression of human leukocyte antigen (HLA)-DR. In BAL the population of CD3+ and CD4+ cells were reduced in SCLC and the T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas these two latter groups did not differ from each other. The distribution pattern of CD16, TF receptor and IL-2 receptor in the study groups resembled that of cells of the blood stream, but CD16+ natural killer cells were additionally down regulated to control values in SCLC. No differences were seen in the distribution of VLA-1. HLA-DR+ cells were clearly elevated in both cancer groups. In general NSCLC was associated with a shift to higher relative numbers of immunocompetent and activated cells. This was most probably attributable to an immune response to neoplastic growth. This shift was largely lacking in SCLC. The analysis of lymphocytes from the periphery of the target organ emerged as a sensitive tool for the study of cellular immunity in lung cancer and showed many similarities to circulating blood cells. However, the analysis of natural killer cells and HLA-DR suggested a dissection of cellular immune response between blood and lung in pulmonary cancer. A depressive interaction between the tumor and the cellular host immune response may contribute to the exceptional malignancy of SCLC.
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  • 7
    ISSN: 1432-1440
    Keywords: Sarcoidosis ; Immune response ; Activity markers ; Soluble CD 14 ; Serum neopterin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups according to disease activity and therapy. The soluble interleukin-2 receptor in serum and the CD4/CD8 ratio in lavage fluid were used to monitor T-lymphocyte activation. No significant differences in serum or bronchoalveolar lavage levels of soluble CD14 were observed in patients with active or inactive sarcoidosis. Despite the presence of normal soluble CD14 serum concentrations a correlation with serum neopterin and angiotensin-converting enzyme was found in active sarcoidosis (soluble CD14 versus neopterin, r s = 0.61 and 0.65, P〈 0.05 and 0.01, respectively; soluble CD14 versus angiotensin-converting enzyme, rs=0.6 and 0.72, P〈 0.02 and 0.003, respectively). A correlation between soluble CD14 and parameters of T-cell activity was not demonstrated. We therefore conclude that soluble CD14 in serum is not a useful clinical parameter in establishing disease activity in sarcoidosis. Neopterin and angiotensin-converting enzyme serum concentrations are parameters with higher sensitivity, although specificity remains very low. The exact role of CD14 antigen in sarcoidosis requires further investigation.
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  • 8
    ISSN: 1432-1750
    Keywords: Key words: Soluble ICAM-1—Sarcoidosis—TNF-α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The soluble form of intercellular adhesion molecule-1 (sICAM-1) might be a serum parameter of inflammatory activity gauging cellular interactions with possible relevance in sarcoidosis. To address this question we measured sICAM-1 by enzyme-linked immunosorbent assay in serum and shedding of this molecule by bronchoalveolar lavage (BAL) cells in sarcoidosis patients (44 and 40, respectively) and in controls (10 and 19, respectively). Serum concentrations of sICAM-1 (588.3 ± 72.2 ng/ml) and its spontaneous release by BAL cells (9.9 ± 1.5 ng/ml) in patients with active sarcoidosis were significantly higher than in those with inactive disease or controls, although no correlation was observed. Significant correlations of sICAM-1 shedding by nonstimulated BAL cells with the serum level of neopterin and of shedding by lipopolysaccharide-stimulated BAL cells with percentage of alveolar macrophages were observed in active sarcoidosis. Kinetic cell culture experiments with peripheral blood mononuclears disclosed a rapid up-regulation of sICAM-1 shedding and tumor necrosis factor-α release; however, at 5 h after stimulation a dissociation of their releases was observed. sICAM-1 release was maintained over 2 days, whereas tumor necrosis factor-α release peaked at 5 and ceased after 43 h. These results provide evidence that circulating and BAL cell culture-derived sICAM-1 reflect the stage of sarcoid inflammation. Although sICAM-1 in BAL cell supernatants originates from alveolar macrophages; the absence of a correlation with serum sICAM-1 concentration indicates that other cells are additional sources of the circulating pool of this molecule.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1750
    Keywords: Alveolar macrophages ; Air pollution ; Nitrogen dioxide ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 cytokines. IL-1β, IL-6, and IL-8 were quantified by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF-α was determined with a “sandwich” ELISA, using the biotin-streptavidin system. NO2 exposure of nonstimulated AM did not result in changes in IL-1β, IL-6, TNF-α, and TGF-β release, compared to the situation with control experiments. Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1β, IL-6, IL-8, and TNF-α (p 〈 .05). The release of TGF-β was not significantly affected by NO2 exposure. Cytotoxicity of AM was checked by trypan blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposure of LPS-stimulated AM resulted in a functional impairment of AM after NO2 exposure regarding IL-1β, IL-6, IL-8, and TNF-α. Neither the spontaneous nor the stimulated release of TGF-β were influenced by NO2.
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  • 10
    ISSN: 1432-1750
    Keywords: Sarcoidosis ; Compartmentalization ; Interleukin-6 ; Tumor necrosis factor α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alveolitis of sarcoidosis is characterized by activated alveolar macrophages (AMs) and T cells. The mediators interleukin-1 (IL-1) and interleukin 6 (IL-6) released by AMs represent essential factors for the progression of the T cells in the cell cycle. The role of IL-1 in pulmonary sarcoidosis has previously been studied; however, the relevance of other mediators (i.e. IL-6) has not yet been evaluated. We measured the spontaneous and lipopolysaccharide (LPS)-induced release of IL-6 and tumor necrosis factor a (TNFα) by bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMNC) in 6 control subjects (group A) and in 15 patients with sarcoidosis, 10 with active (group B), 5 with inactive disease (group C). IL-6 as well as TNFα were spontaneously released by BAL cells of the active group in significantly greater amounts compared to both other groups; IL-6: A, 165.5 pg/ml/24 hr/106 cells (range, 0–604), B, 946 (0–2467), C, 16.6 (0–83); TNFα: A, 162 pg/ml/24 hr/106 cells (0–523), B, 803 (100–17352), C, 100 (0–379). In all groups autologous PBMNC proved to be quiescent, releasing only baseline levels of the cytokines tested. After stimulation with LPS all these cells released great quantities of IL-6 and TNFα. In active disease a positive correlation between IL-6 and TNFα release was observed (r = 0.77, p 〈 0.02). The present study documents that in active sarcoidosis the spontaneous release of IL-6 by BAL cells parallels the spontaneous release of TNFα. IL-6 is capable of initiating the proliferation and activation of T cells in the lung.
    Type of Medium: Electronic Resource
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