PubMed Health⌕ Search

Biomedical subjects

W Schmutzler

Publications and source records attributed to W Schmutzler.

At least 19 recordsLinked to original sources
PubMed1999

Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells.

OBJECTIVES AND DESIGN: The effects of the mucolytic agents ambroxol and N-acetylcystein (NAC) were studied on the release of histamine, leukotrienes, cytokines and superoxide anions from a variety of cells involved in the pathogenesis of allergic inflammation. SUBJECTS: Mast cells were isolated from human adenoids and skin (n = 5-6). Basophils, monocytes and granulocytes were obtained from Buffy-coat blood obtained from healthy blood donors (n = 4-7) and enriched by density centrifugation. TREATMENT AND METHODS: Ambroxol or NAC were added to the cells for different periods before stimulation with various immunological and non-immunological secretagogues. Histamine release from mast cells, basophils and monocytes was assayed either by radioimmunoassay or spectrofluorometrically. LTC4 (basophils), LTB4 (neutrophil/eosinophil granulocytes or monocytes), IL-4 and IL-13 (basophils) were measured by ELISA. RESULTS: Ambroxol inhibited histamine release by more than 50% from human adenoidal mast cells (1000 microM ambroxol) and skin mast cells (100 microM ambroxol) stimulated by Con A and compound 48/80, respectively. Ambroxol (100 microM) strikingly inhibited anti-IgE induced release of both histamine, LTC4, IL-4 and IL-13 from basophils and reduced both histamine and LTB4 release induced by C5a or Zymosan in monocytes. The drug also reduced LTB4 and superoxide anion production in granulocytes stimulated by zymosan or fMLP. In all cell types studied, ambroxol was more efficacious following a short preincubation (5-15 min) of the drug with the cells before stimulation. In contrast, NAC produced no clear effects on any of the different cell types studied, regardless of the preincubation period, the concentration or the stimulus employed. CONCLUSIONS: Unlike NAC, ambroxol is able to not only inhibit acute mediator release from mast cells and leukocytes but also reduce immunomodulatory cytokine generation from basophils and may have beneficial effects in the treatment of allergic respiratory diseases.

Ambroxol↗
PubMed1998

Generation and subcellular distribution of histamine in human blood monocytes and monocyte subsets.

OBJECTIVE AND DESIGN: This study was designed to establish the sites of formation and storage of histamine and histidine decarboxylase (HDC) in human monocytes and two of their subsets. MATERIALS AND METHODS: The experiments were carried out using monocytes from buffy coats of healthy blood donors. Histamine was quantitated by RIA, HDC activity by the formation of histamine. RESULTS: The monocyte subtype RM3/1 contained significantly more histamine than the subset 27E10 (0.041+/-0.025 vs. 0.005+/-0.004 pg/cell, p < 0.05) and also more HDC activity and HDC mRNA. After fractionation of monocyte homogenates in a discontinuous Percoll gradient or by differential centrifugation more than 80% of both, HDC activity and histamine, were recovered from the cytosolic fractions. About 50% of this histamine was found to be bound to proteins. CONCLUSIONS: In monocytes histamine and HDC are colocalized in the cytoplasm indicating a subcellular distribution different from mast cells or basophils. The data also show that histamine is synthesized by the monocytes themselves.

Cell Fractionation↗
PubMed1998

The effects of the glucocorticoids prednisolone, deflazacort and beclomethasone-dipropionate on the RM 3/1 macrophage in human peripheral blood.

Different glucocorticoids (GC) applied intravenously, subcutaneously or in vitro exert only small differences in the ability to raise RM 3/1 macrophages from human blood monocytes. Dermal application however reveals a dose-dependent difference between GC. The present experiments were designed to study the efficacy of oral and topical application in this model. We also intended to obtain some information about the qualitative differences between the effects of prednisolone and deflazacort, which was reported to cause less adverse reactions than other GC. Both GC were orally administered to probands in doses regarded as equivalent with respect to general GC effects by the manufacturers of deflazacort (5-6 mg or multiples). A single dose of 5 mg prednisolone had no effect; 50 mg increased the number of RM 3/1 macrophages within 12 h from a basal level of 8.5% to about 80% similar to an intravenous or subcutaneous administration of GC. 10 mg prednisolone enhanced the number of RM 3/1 macrophages also within 12 h, reaching a mean maximum of about 60% at 24 h, declining thereafter. 12 mg deflazacort raised the number of RM 3/1 macrophages much slower, reaching a maximum of 30% (average) after 48 h. The interindividual variation was found to be mainly the time lag between dosage and maximum effect. Interindividual differences of prednisolone effects concerned mainly the maximal increase of RM 3/1 macrophages after 24 h. These results show that in this test system deflazacort was found to be less effective than expected. To elucidate the topical influence of GC, probands inhaled twice daily 0.5 mg beclomethasone-dipropionate over a period of 11 days. No effect on the number of RM 3/1 macrophages was observed, suggesting that beclomethasone applied in this dose did not cause systemic GC reactions.

Administration, Inhalation↗
PubMed1995

Alteration in the pattern of macrophage subtypes in chronic osteomyelitis compared with acute joint infection.

Macrophage subtypes were detected in cryostat sections of biopsies from patients with chronic osteomyelitis, acute joint infections and normal bone marrow, using monoclonal antibodies against different macrophage populations. The resident macrophage subtype 25F9, the gluco-corticoid-inducible macrophage RM 3/1 and the inflammatory type 27E10 were found in abundance in acute infections. They were also present in tissue sections of uninflamed bone marrow. By contrast, in about 50% of the biopsies from patients with chronic osteomyelitis a reduced number of macrophage subtypes, or even the lack of one or more macrophage subpopulations was found. The unusual absence of macrophage phenotypes seems to be restricted to the area of osteomyelitis because in the tissues of inflamed sinuses in these patients, the macrophage subtypes were present. These findings suggest a disturbance at the level of the macrophages which may contribute to the persistence of the inflammatory process in osteomyelitis.

Acute Disease↗
PubMed1995

Characterization of a novel anti-inflammatory factor produced by RM3/1 macrophages derived from glucocorticoid treated human monocytes.

Glucocorticoids exert their anti-inflammatory activity by modulating the functions of various cell types including macrophages. They also induce the generation of a distinct macrophage subtype defined by the surface antigen RM3/1 which appears to be associated with the down-regulation of inflammation. Supernatants from these cells were found to exert a dose-dependent anti-inflammatory effect, particularly in the early phase as shown in the 5-hydroxytryptamine (5-HT) induced footpad edema of mice. By using conventional purification methods the anti-inflammatory factor was found to have a molecular mass of about 78 kD and an isoelectric point of about 7.9. Heat lability and sensitivity to trypsin and proteinase K indicate the protein nature of the anti-inflammatory factor. The inhibition of the early phase of inflammation and the molecular weight suggest that the anti-inflammatory agent released from RM3/1 macrophages is a novel protein different from other anti-inflammatory proteins described so far.

Animals↗
PubMed1994

Macrophages and lymphocytes: alternative sources of histamine.

Some recent observations have indicated that cells other than mast cells, notably macrophages, may contain significant amounts of histamine. Using a histamine-specific radioimmunoassay, we found that human blood monocytes and lymphocytes contain about 0.05 pg histamine/cell. Various other cells, e.g. fibroblasts, colorectal tumor, kidney and ovarian cells, and murine bone marrow derived macrophages contained markedly less histamine (< 0.008 pg/cell). Ionophore A23187 (1 microM) released up to 50% of the total histamine from monocytes and lymphocytes. C5a caused a dose-dependent histamine release of up to 40% in monocytes and up to 20% in lymphocytes. Substance P induced a release only in cells of certain donors. Lipopolysaccharide, concanavalin A, and compound 48/80 had no effect. Culturing of the cells caused a loss of cellular histamine and its releasability. In view of the huge numbers of monocytes and lymphocytes in the blood, the histamine in these cells has to be taken into account under both physiological and pathophysiological conditions.

Cells, Cultured↗
PubMed1994

Inhibition of spontaneous and mitogen-induced lymphocyte proliferation by murine bone marrow-derived macrophages: role of prostaglandins, nitric oxides and cell-to-cell contact.

Spontaneous and mitogen-stimulated proliferation of spleen lymphocytes was inhibited by coculturing the cells with murine bone marrow derived macrophages (BM-M phi). The inhibitory effect was found to be dependent on the maturation stage of BM-M phi reflected by the appearance of the phenotype BM 8 and on the number of BM-M phi added to the lymphocytes. The spontaneous proliferation was only inhibited by the addition of high numbers of BM-M phi of late maturation stage. The lipopolysaccharide (Lps) induced response was strongly suppressed by increasing proportions of BM-M phi of either cultivation stage. The suppressive effect on the concanavalin A (Con A)-induced proliferative activity increased with the maturation of the macrophages. Inhibition of prostanoid release with indomethacin had no effect. Blocking of nitric oxide synthesis partially reversed the inhibitory effect of macrophages mainly on the Con-A response. Addition of culture supernatant of BM-M phi to the lymphocytes did not mimic the effect of the macrophages themselves. BM-M phi only slightly inhibited the proliferation when lymphocyte-BM-M phi cell-to-cell contact was prevented. These results show that BM-M phi differently influence the spontaneous and mitogen-induced lymphoproliferation and that the inhibitory effect of BM-M phi on the lymphocyte proliferation is only partially mediated by secretory products of macrophages but apparently requires cell-to-cell contact between both cell types.

Animals↗
PubMed1992

Influence of dexamethasone on the RM 3/1-positive macrophages in the peripheral blood and tissues of a New World monkey (the marmoset Callithrix jacchus).

Subcutaneous injection of the glucocorticoid dexamethasone in the primate Callithrix jacchus increased the proportion of the macrophage subtype RM 3/1 in the blood from a basic level of 16% positive monocytes to about 65%. The elevated numbers of RM 3/1-positive cells were seen 24 and 72 h after application and were independent of the dosages used (50 or 150 micrograms/kg). Oral administration had no effect. CD4-, CD14- and CDw14-antigen expression of monocytes was not influenced by the dexamethasone treatment. In tissues, e.g. spleen, thymus, liver, skin and kidney, RM 3/1-positive macrophages revealed a similar distribution as in human tissues but no differences in glucocorticoid treated to control animals could be observed. These results show that glucocorticoids induce in the monkey Callithrix jacchus a distinct monocyte subtype similarly as in man while other macrophage phenotypes were not influenced.

Animals↗
PubMed1991

The influence of H1-, H2- and H3-receptors on the spontaneous and ConA induced histamine release from human adenoidal mast cells.

The effects of the H3-agonist R-alpha-methylhistamine (R-alpha-MeHA) and the H3-antagonist thioperamide on the spontaneous and concanavalin A (ConA) induced histamine release from human mast cells were tested and compared with the effect of some H1- and H2-receptor active substances. R-alpha-MeHA (10(-9)-10(-7) M) exerted no effect on histamine release whereas thioperamide increased the spontaneous release at 10(-6)-10(-4) M but inhibited the ConA induced release in a narrow concentration range (10(-6)-10(-5) M). This enhancement might be taken as an indication of the existence of H3-receptor dependent autoregulation although presently other mechanism cannot be excluded.

Adenoids↗
PubMed1991

Comparison of dermal and systemic application of glucocorticoids on the RM 3/1+ macrophage in human blood.

Dermal administration of either hydrocortisone or fluprednidene to healthy skin causes only a weak and short-lasting increase of the proportion of the anti-inflammatory macrophage RM 3/1 in the blood compared to the effect of the systemic application of glucocorticoids on this cell subtype. On the other hand, a rather permanent increase of these macrophages could be observed in untreated patients suffering from certain skin diseases, e.g. urticaria, atopic dermatitis, psoriasis.

Administration, Cutaneous↗
PubMed1990

Effects of calmodulin antagonists on human adenoidal mast cells.

N-(6-aminohexyl)-1-naphthalenesulfonamide (W5), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and Triflupromazine (TFPr) are substances with calmodulin antagonistic properties. All of these compounds inhibited the Con A-induced histamine release from human adenoidal mast cells. Maximal inhibition for W5 was observed at 200 microM, for W7 at 50 microM and for TFPr at 20 microM. Higher concentrations of each substance induced a marked histamine release. The kinetics of the mediator release were found to be different for Con A and W7 only after 5 mins incubation. The kinetics of TFPr were found to be biphasic: a slow onset was followed by a fast release reaction.

Adenoids↗