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J Müller-Quernheim

Publications and source records attributed to J Müller-Quernheim.

At least 91 records · Page 5Linked to original sources
PubMed1996

Anti-inflammatory cytokine release by alveolar macrophages in pulmonary sarcoidosis.

Sarcoidosis is a systemic, granulomatous disorder with a high rate of spontaneous remission indicating the presence of antiinflammatory mechanisms. Antiinflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) should be able to induce spontaneous remission of sarcoidosis. By measuring the release of both mediators in culture supernatants of bronchoalveolar lavage (BAL) cells, we investigated their relevance in the spontaneous remission of sarcoidosis. No spontaneous IL-10 release was observed by BAL cells of sarcoid patients. In supernatants of BAL cells of seven patients found retrospectively to be free of any interstitial lung disease, we found 612 +/- 261.2 pg/ml (mean +/- SEM) TGF-beta. TGF-beta release was recorded in 20 of 39 patients with active disease. Patients with active disease without TGF-beta release in BAL cell culture either required therapy (n = 21; 677 +/- 159 pg/ml) or showed evidence of persisting disease (n = 6; 762 +/- 419 pg/ml). Patients with active disease without indications for therapy and with significantly increased TGF-beta release (n = 12; 1,422 +/- 215 pg/ml; p < 0.004 in all comparisons) had a spontaneous remission within 6 mo. Increased TGF-beta release (1,560 +/- 353 pg/ml) was observed in five of five patients receiving therapy. We conclude that TGF-beta is a regulator of the inflammatory process in sarcoidosis.

Adrenal Cortex Hormones↗
PubMed1995

[Prognosis of sarcoidosis].

Sarcoidosis is a frequent, systemic, granulomatous disorder with predominant involvement of the hilar lymph nodes and the pulmonary parenchyma. By bronchoalveolar lavage an activation of alveolar immune cells has been observed yielding a detailed concept of the immunopathogenesis of the disease from which new, clinically applicable staging parameters are delineated. There is some evidence that immunopathogenetic mechanisms determine the course and the prognosis of the disease.

Adrenal Cortex Hormones↗
PubMed1995

[Activation of immune cells in sarcoidosis: immunopathogenic and clinical implications].

Sarcoidosis is a frequent, systemic, granulomatous disorder with predominant involvement of the hilar lymph nodes and the pulmonary parenchyma. By bronchoalveolar lavage an activation of alveolar immune cells has been observed yielding a detailed concept of the immunopathogenesis of the disease from which new, clinically applicable staging parameters are delineated.

CD4-CD8 Ratio↗
PubMed1995

[Sarcoidosis: immunopathology and criteria of biological activity].

In France, sarcoidosis is the most frequent interstitial lung disease of unknown origin. Its prevalence is about 9.5 in 100 000. Almost 30% of the patients require corticosteroid treatment. Although the aetiology remains unknown, detailed concepts of the immunopathogenesis have been suggested. Employing the technique of bronchoalveolar lavage, some immunopathogenic mechanisms have been elucidated and the hypothesis that an unknown causative agent stimulates T-lymphocytes and macrophages by physiological mechanisms has emerged. The activity of these cells maintains the inflammation and is the target of the corticosteroid therapy. By new serologic parameters it is possible to gauge this activity and to document the therapeutic effect.

Anti-Inflammatory Agents↗
PubMed1994

[The chemotactic behavior of alveolar macrophages and blood monocytes after exposures to different NO2 concentrations].

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 chemotactically active agent. The number of AM or BM which actively migrated through the polycarbonate membrane under the influence of C5a was measured by means of a light microscope. The migration rate of AM (compared to air exposure) was reduced by 33% with 1.0 ppm NO2 and by 61% with 5.0 ppm. The migration rate of BM in similar conditions was reduced by as much as 55%. There was no significant cytotoxic effect of NO2 exposure at 1.0 and 3.0 ppm. With 5.0 ppm 13.0 +/- 3.0 cells were no longer viable. These results indicate that NO2 concentrations relevant to indoor conditions affect the chemotaxis of AM and BM after short-time NO2 exposures. The data further suggest that NO2 exposures of these cells depressed chemotactic mechanisms without relevant cytotoxicity.

Aged↗
PubMed1994

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 time between 30 and 120 minutes and concentrations between 0.3 and 1.5 ppm SO2 were chosen for exposure. Thirty minutes exposure of AM to SO2 (0.3-1.5 ppm) yielded a dose-dependent stimulation of ROI release; 2.0- to 3.6-fold of control (r = 0.965, p < 0.005). An exposure of 120 minutes to SO2 resulted in a similar ROI production of about 2.5-fold at all tested concentrations. These experiments provide evidence that AM and PBMNC become activated by SO2 producing large amounts of ROI.

Bronchoalveolar Lavage Fluid↗
PubMed1994

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 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 SO2 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.

Adult↗
PubMed1994

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 SO2. Higher SO2 concentrations caused a further impairment of MCA as well as a dose-dependent decrease in CBF (P = 0.002). A concentration of 12.5 ppm SO2 induced a decrease from baseline values of approximately 80% in mean MCA and of roughly 70% in mean CBF. This study demonstrates a dose-dependent SO2-induced decrease in MCA of guinea pig tracheas. The decrease in MCA was associated with an impairment of CBF only at SO2 concentrations higher than 5.0 ppm.

Animals↗
PubMed1994

Beryllium-induced disturbances of the murine immune system reflect some phenomena observed in sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin. In respect to clinical and immunological characteristics, it is indistinguishable from berylliosis. As an approach to develop a murine model reflecting some aspects of sarcoidosis, we attempted to induce berylliosis in mice by treating inbred F1 mice (C57B16 x DBA/2) with 3 mg beryllium sulfate (BeSO4) per kg body weight intraperitoneally. Either pure BeSO4 or BeSO4 in combination with incomplete Freund's adjuvant was administered. Alternatively, pure BeSO4 was injected 2 days after a single application of cyclophosphamide (150 mg/kg). The spleen index, the spontaneous and phorbolmyristate acetate (PMA)-induced radical oxygen intermediates (ROI) released by peritoneal macrophages, and the proliferative activity of spleen mononuclear cells in response to BeSO4 and concanavalin A (ConA) were evaluated and compared to the corresponding changes observed in sarcoidosis. In all three modes of BeSO4 treatment, the spontaneous ROI release by peritoneal macrophages was significantly elevated. These elevations were very similar to those observed with alveolar macrophages in active sarcoid alveolitis. After BeSO4 treatment, a small proliferative activity of spleen mononuclear cells in response to BeSO4 could be observed. Further, BeSO4-treated spleen mononuclear cells exhibited a markedly reduced response to ConA stimulation (approximately 20% of control) which parallels the reduced proliferative capacity of sarcoid peripheral blood mononuclear cells (approximately 45% of control). This reduction could be abolished by pretreating the mice with cyclophosphamide. BeSO4 treatment in combination with incomplete Freund's adjuvant resulted in a significant increase of spleen mononuclear cell proliferation (1.9-fold) after in vitro stimulation with BeSO4, and prevented the low responsiveness to ConA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Subtyping of T-lymphocytes in sarcoidosis].

Sarcoidosis is characterised by a T-helper cell-alveolitis. Phenotyping of T-cells of bronchoalveolar lavage (BAL) and of peripheral blood was performed with antibodies directed against naive T-cells (CD45RA+), memory T-cells (CD45R0+), alpha beta T-cell antigen receptor (TCR) bearing cells and gamma delta T-cell antigen receptor bearing cells in 11 patients with active sarcoidosis, 5 patients with inactive sarcoidosis, 5 patients with idiopathic pulmonary fibrosis (IPF), and in control individuals (7 for BAL and 21 for peripheral blood). In peripheral blood one third of sarcoidosis patients exhibited increased (< 12%) numbers of TCR gamma delta+ cells. The corresponding numbers of BAL were within the normal range. More than 95% of alveolar T-helper cells in sarcoidosis, in IPF, and in controls could be identified as memory T-cells (CD45R0+). In comparison to controls in the peripheral blood of sarcoidosis and IPF patients a small, not-significant shift towards memory T-cells was observed. The immunophenotypical markers evaluated in BAL and peripheral blood did not yield parameters for the clinical staging of the investigated diseases.

Antigens, CD↗
PubMed1994

[In vitro studies of modification of mucociliary clearance by guinea pig tracheas by exposure to air pollutants of sulfur or nitrogen dioxide].

We studied the effect of sulfur dioxide (SO2) and nitrogen dioxide (NO2) on mucociliary activity (MCA) and ciliary beat frequency (CBF) in 63 guinea pig tracheas. The tracheas were placed in a gas cylinder and exposed for 30 minutes to SO2 concentrations ranging from 2.5 to 12.5 ppm or to NO2 concentrations ranging from 3.0 to 15.0 ppm. Control experiments were performed with exposure of the tracheas to synthetic air. MCA was measured by recording the light reflected from ciliated mucous membranes using an infrared barcode reader and CBF using video-interference microscopy. The exposure to 2.5 ppm SO2 caused a reduction in mean MCA of 63% and no significant changes in CBF. Higher SO2 concentrations caused a further impairment of MCA as well as a dose-dependent decrease in CBF. 10.0 or 12.5 ppm SO2 induced a decrease from baseline values to approximately 20% in MCA and to roughly 30% in mean CBF. The exposure to NO2 at concentrations ranging from 3.0 to 15.0 ppm did not induce any changes in MCA or CBF of the guinea pig tracheas. Our results show that exposure to SO2 for 30 minutes is able to depress the mucociliary clearance of guinea pig tracheas, whereas the exposure to equivalent NO2 concentrations for the same time do not alter the mucociliary transport.

Air Pollutants↗
PubMed1994

[Extrapulmonary manifestation of sarcoidosis in the breast].

Sarcoidosis is, pathologico-anatomically speaking, a granulomatous disease that can involve almost any organ. However, a histologically confirmed involvement of the mammary gland after exclusion by differential diagnosis of granulomatous mastitis and mycobacterial or fungal sonographic and mammographic image would rather suggest a fibroadenoma of the breast. However, a malignant process such as for instance a mucinous carcinoma of the breast should always be excluded by differential diagnosis, especially if there are concomitant general symptoms of disease.

Aged↗
PubMed1994

[Monitoring sarcoidosis therapy with immunopathologic parameters].

Recently a detailed concept of the immunopathogenesis of sarcoidosis has been developed. Some components of this concept can be explored by means of simple serological or bronchoalveolar parameters allowing staging of the inflammatory activity of the disease and control of the therapeutical effectiveness. Serum neopterin and the serum level of the soluble interleukin-2 receptor are useful in assessing the activity of macrophages/monocytes and of T-lymphocytes, respectively. Bronchoalveolar lavage yields different cytological patterns typical for the acute and chronic forms of the disease permitting the identification of the subpopulation on risk for functional deterioration.

Bronchoalveolar Lavage Fluid↗
PubMed1994

[Toxic lung damage caused by mitomycin C].

Lung toxicity is one of the rare side effects of mitomycin C (MMC), an effective antineoplastic agent. There have been only few reports on pulmonary damage after MMC monotherapy. We describe a case of a pulmonary reaction following MMC monotherapy. The patient was examined including bronchoalveolar lavage (BAL) and transbronchial lung biopsy. BAL yielded the diagnosis of a lymphocyte alveolitis with normal CD4/CD8 ratio within the T lymphocytes. Histologically a florid alveolitis was diagnosed. Radiological and CT findings including HR-CT are described.

Aged↗
PubMed1993

[In vitro studies of the beat frequency of ciliary cell cultures after short-term exposure to SO2 and NO2].

Mucociliary transport is an important defense mechanism of the respiratory tract. The aim of this study was to investigate the effect of SO2 and NO2 at different concentrations on ciliary beat frequency (ZSF). Single ciliated cells were obtained from 25 volunteers by nose brush. ZSF was quantified using video-interference-microscopy. The cells were placed on a polycarbonate membrane, which was in contact with the surface of a reservoir filled with RPMI medium (bicarbonate buffered) or electrolyte solution (Ringer), allowing the cells to be supplied by capillarity. In an exposure chamber the cells were exposed for 30 to 120 min to SO2 2.5 to 15.0 ppm at 37 degrees C. SO2 induced a dose dependent decrease in ZSF of the cells, supported by Ringer solution. 2.5 ppm SO2 caused a 42.8%, 12.5 ppm a nearly 100% decrease (8.10 +/- 0.24 vs. 0.28 +/- 0.20 Hz). ZSF of cells cultured in RPMI medium was reduced moderately after 12.5 ppm SO2 exposure (7.90 +/- 0.26 vs. 6.66 +/- 0.31 Hz). In Ringer solution we observed a decrease of pH after 30 min SO2 exposure with 12.5 ppm to a minimum value of 3.6. In marked contrast, the pH of RPMI medium remained constant at 7.5 under identical conditions. After adding RPMI medium to Ringer solution, ZSF increased in parallel to the pH (5.0 ppm: 2.77 +/- 0.37 to 7.97 +/- 0.49 Hz). After an initial increase in ZSF, 120 min NO2 exposure to 15.0 ppm yielded a decrease in ZSF of 23.3% under conditions of constant pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Increased interleukin 6 production by bronchoalveolar lavage cells in patients with active sarcoidosis.

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 alpha (TNF alpha) 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 TNF alpha 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/10(6) cells (range, 0-604), B, 946 (0-2467), C, 16.6 (0-83); TNF alpha: A, 162 pg/ml/24 hr/10(6) 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 TNF alpha. In active disease a positive correlation between IL-6 and TNF alpha 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 TNF alpha. IL-6 is capable of initiating the proliferation and activation of T cells in the lung.

Adult↗