Search

Im Maximilianmuseum in Augsburg findet im ‚Maximiliansjahr‘ 2019 die Ausstellung „Maximilian I. (1459-1519). Kaiser. Ritter. Bürger zu Augsburg“ statt. Die Ausstellung beherbergt außer hochwertigen Leihgaben auch ein besonderes Highlight: In einer virtuellen Umgebung werden längst abgerissene Stadttore computergestützt nachmodelliert und für die Besucher wieder zugänglich, obwohl die Originale schon lange nicht mehr Teil des Stadtbildes sind. Eines davon war einst eine berühmte Touristenattraktion: Augsburgs ‚Alter Einlass‘, das Nachttor, erbaut 1514 angeblich für Kaiser Maximilian I. Abgerissen wurden die letzten Überreste der großflächigen Anlage 1867. Besonders die komplexen Mechaniken im Inneren des Durchgangs waren weithin berühmt und können nun durch penible wissenschaftliche Recherche und Virtual-Reality-Brillen wieder erfahrbar gemacht werden. Augsburg‘s Maximilianmuseum, which is not only the city’s art-historical museum but also includes the history of the town, will be home to an exhibition themed around Emperor Maximilian Ist in the third quarter of 2019. Within the exhibition there is one very special highlight to be found: Embedded in a virtual-reality-environment, two of the city’s historical gates are getting a computer-based re-modeling and will be opened for visitors, even though the original buildings were torn down many years ago. The larger of those gates, the ‚Alter Einlass‘ of Augsburg, an entrance to the city erected in 1514, was initially built for Emperor Maximilian Ist. The last remains of this complex building were torn down in 1867. Once famous for its hidden mechanics, the famous portal can now be experienced once again through virtual-reality-glasses., MEMO Medieval and Early Modern Material Culture Online; Volume 2019 (4); Seitenzahl: x; ISSN: 2523-2932

Die vorliegende Ausgabe nimmt den 500. Todestag Kaiser Maximilians I. zum Anlass, das Thema „Gedächtnis und Gedenken“ aufzugreifen. In ihr versammeln sich Forschungsbeiträge aus den Bereichen Kunstgeschichte, Bauforschung, Museumswissenschaften, Archäologie und Geschichtswissenschaft, die sich mit der Funktion von Objekten als Medien der Erinnerung in historischen Kontexten auseinandersetzen. Mit Beiträgen von Heidrun Lange-Krach, Christoph Emmendörffer, Christoph Hauptmann, Ilja Sallacz, Chassica Kirchhoff, Nina Stainer, Jochen Vennebusch, Claudia Theune und Iris Winkelbauer. Elisabeth Gruber, Gabriele Schichta: Editorial; Jochen Hermann Vennebusch: „Du, geliebter Leser, erbarme dich zugleich unser“ – Der „Hillinus-Codex“ (Cod. 12) als mehrschichtiges Erinnerungsobjekt; Chassica Kirchhoff: Memories in Steel and Paper: A Spectacular Armor and its Representation In Early Modern Augsburg; Heidrun Lange-Krach, Christoph Emmendörffer, Christoph Hauptmann, Ilja Sallacz: Ein neuer Weg zur Stadtgeschichte – Virtual Reality im Maximilianmuseum; Claudia Theune, Iris Winkelbauer: Erinnerung an Maximilian I. auf Schloss Hanfelden in der Steiermark; Nina Stainer: Der Weg der Zeichnung. Die Handzeichnung als Medium der Kommunikation, Erinnerung und Selbstzeugnis des Bildhauers im 17. Jahrhundert, MEMO Medieval and Early Modern Material Culture Online; Volume 2019 (4); Seitenzahl: x; ISSN: 2523-2932

Pulmonary infections are important causes of morbidity and mortality in immunosuppressed patients after transplantation. After experimental irradiation and syngeneic bone marrow transplantation in mice, macrophages show reduced repopulation in the lung compared with that in other tissues. Macrophages are major microbicidal immune effector cells in host pulmonary defense. Therefore, we examined the role of locally applied cytokines for macrophage repopulation in the lung. An accelerated repopulation of macrophages in the lung was observed after intranasal application of macrophage-colony stimulating factor (M-CSF), but this effect was not enhanced by a combination of M-CSF with interleukin (IL)-3. Local proliferation contributed to this effect. Macrophages in the lung tissue of M-CSF-treated mice displayed greater secretion of IL-6, whereas M-CSF treatment did not enhance the gene expression of other macrophage-specific chemokines. The role of M-CSF treatment was determined in pulmonary murine cytomegalovirus infection using an irradiation/reconstitution model. The M-CSF treatment had no effect on virus load in the lung tissue. However, phosphate-buffered saline-treated mice seemed to develop stronger inflammation after viral infection than M-CSF-treated mice. We conclude that local M-CSF treatment modulates cellular inflammation in the lung during immunosuppression.

Pulmonary macrophages play a crucial role in the defense of inhaled pathogens. We characterized functional properties of alveolar (AM) and interstitial (IM) macrophages from rats. AM exhibited a pronounced microbicidal capacity as shown by an elevated production of reactive oxygen intermediates (ROI), nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and tumor cytotoxicity when compared with IM. In contrast, IM were superior to AM regarding mechanisms mainly involved in the induction and maintenance of specific immune reactions (major histocompatibility complex [MHC] class II expression, interleukin [IL]-1 and IL-6). In this line, we were interested in whether the microbicidal potential of AM could be augmented by treating Lewis rats with rat recombinant interferon (IFN)-gamma (5 x 10(2) to 1 x 10(5) U/animal) intratracheally, avoiding infection of interstitial lung macrophages or other organ-associated macrophages. The pulmonary cytokine application resulted in an activation of AM when macrophages from IFN-treated animals were compared with control macrophages from saline-treated rats 18 h after the treatment: (1) mediator release (ROI, NO, TNF-alpha, IL-6), (2) tumoricidal activity; (3) dose-dependent increase of MHC class II expression. The local immunomodulation enhanced the resistance of normal and immunosuppressed rats against respiratory infections with Listeria monocytogenes. Taken together, local activation of lung macrophages is a feasible therapeutic strategy against pulmonary infections.

Activation of autoreactive T-lymphocytes by cultured syngeneic glomerular mesangial cells. The capacity of intrinsic, glomerular mesangial cells (MC) to cause an autoreactive response of syngeneic lymphocytes in vitro are presented. Initial experiments demonstrated the MHC class II dependent capacity of MC to present exogenous antigen to sensitized lymph node lymphocytes (LN) and to activate naive, allogeneic LN in the absence of a nominal antigen. However, the most striking finding of the present investigation was that mouse MC (C57BL/6 or DBA/2) augmented a significant activation of naive, syngeneic lymphocytes. The extent of the proliferative lymphocyte response was comparable to that observed after stimulation with allogeneic MC. Moreover, during syngeneic coculture substantial amounts of interferon bioactivity were generated. Equipotent concentrations of rm IFN-γ were sufficient to induce class II MHC expression of mouse MC. In control experiments the macrophage cell line, IC-21 (C57BL/6), or freshly prepared DBA/2 mouse peritoneal macrophages did not elicit a syngeneic LN response. Using MC, which had not been pretreated, the MC-specific LN stimulation occurred after prolonged periods of coculture. The stimulation index (S.I.) was 9.77 after 144 hours compared with LN controls (S.I. = 1). However, a 48 hour pretreatment of MC with either rm IFN-γ alone or in combination with rh TNF-α and/or the continuous presence of rm IL-1α during coculture periods from 72 to 144 hours substantially enhanced the proliferative LN response. Analysis of non-adherent LN by flow cytometry (FACS) after 96 or 120 hours coculture with MC revealed an increased ratio of Thy1.2 + to B220 + cells with a predominant rise of L3T4 + T-helper cells compared to Lyt2 + cytotoxic T-cells. Furthermore, immune fluorescence microscopy showed that a fraction of Thy 1.2 + lymphoblasts adhered to MC. FACS analysis of these adherent LN after detachment demonstrated that in comparison to cocultures with untreated MC, cocultures of LN with IFN-γ/TNF-α pre-treated MC resulted in a 24.4% increase of Thy1.2 + cells, with 89% of these being L3T4 + T-helper lymphocytes. In conclusion, autoreactivity of preferentially T-helper cells to cocultured glomerular MC was shown, which may represent a useful model of T-lymphocyte dependent glomerulonephritis.

During the course of lupus-like autoimmune disease male BXSB mice develop an increasing monocytosis in the peripheral blood. As we demonstrated previously, this monocytosis is parallelled by an expansion of a strain-specific high number of macrophage precursor cells (CFU-M) in the bone marrow of male mice. To test the hypothesis that the expanded mononuclear phagocyte system (MPS) may promote autoimmune disease in these mice the organ-associated macrophage system was examined. Our latest data show that an unusual expansion of CFU-M also appears in spleen and liver of male mice 2 weeks after birth. In addition to a morphological alteration of the organs during the course of the disease there is a change in number and distribution of organ-resident macrophages. Considering these results the possible contribution of the expanded MPS in promoting autoimmune disease is discussed.

MRL-lpr/lpr mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen-presenting as well as cytokine-producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL-lpr mice. Our investigations concerning production of superoxide anion and TNF-α by LPS and/or IFN-γ activated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il-2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL-lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA-autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL-lpr/lpr mice. J. Leukoc. Biol. 57: 242–249; 1995.

Neutrophils from 50 pediatric patients with normal phagocyte functions, from 150 healthy adults, from 10 chronic granulomatous disease (CGD)-patients (4 CGD+), and from 18 X-linked carriers for CGD have been tested for their production of H2O2 using staining with dihydrorhodamine 123 and subsequent flow cytometry. Additionally, neutrophils from three patients with myeloperoxidase deficiency were assessed. Cells were activated to produce H2O2 by the phorbol ester phorbol-myristate-acetate (PMA) and by phagocytosis of Escherichia coli bacteria. To evaluate the sensitivity of the method, H2O2-production by neutrophils which was inhibited by different concentrations of diphenyljodonium (DPI) was measured. The results were compared to those from other methods (NBT-testing, cytochrome c-reduction, and especially chemiluminescence). Normal values and ranges of scatter profile were evaluated in terms of peak channel fluorescence: 97%700, x = 840 +/- 59 (S.D.), 97%890, for pediatric patients. Normal quantitative values also resulted from small blood samples of infants (1 year, n = 6, x = 830 +/- 52). For CGD+ (n = 4) the results were clearly far below the normal range. In indicating decreased production of reactive oxygen intermediates the method was at least as sensitive as lucigenin enhanced chemiluminescence. Cytochrome b558-expression of neutrophils from patients and healthy controls was established by flow cytometry following staining with the monoclonal antibody 7D5. The normal range was 97%485, 97%680, peak channel fluorescence. We conclude that flow cytometric routine diagnostics of CGD can easily enhance the reliability of recognition and the yield of information about this disease compared to conventional methods.

Macrophage precursor cells, derived from mouse bone marrow culture with granulocyte-macrophage colony-stimulating factor or colony-stimulating factor 1 (CSF-1) as growth factor and interleukin-2 (IL-2) as stimulating factor, were activated by IL-2 to exert strong cytolytic activity against Yac-1 cells. In response to IL-2 stimulation these bone marrow macrophage precursor cells produced perforin as lytic molecules. The purity of the precursor cells for the study was proved as homogeneous positivity for Mac-1, NK-1.1 and negativity for Lyt 1 and 2. The cells express CSF-1 receptors on their surface, are able to proliferate and differentiate into typical macrophages when stimulated with CSF-1, and are therefore members of the macrophage lineage. Perforin transcripts were identified by Northern blot analysis of IL-2–treated macrophage precursor cells, and the presence of perforin protein in the cytoplasmic granules was demonstrated by immunhistochemical staining using a monoclonal antiperforin antibody. In addition, the biological activity of the perforin contained in the macrophage precursor’s granules could be documented as calcium-dependent lytic activity using Yac-1 and sheep red blood cells as targets. The results presented in this paper imply the existence of a bipotent precursor cell, which can mature into a typical macrophage if CSF-1 or phorbol 12-myristate 13-acetate is supplied as differentiation stimulating factor but develops into an NK/LAK cell when early activation with IL-2 is provided. J. Leukoc. Biol. 56: 117–123; 1994.

Recently, the diagnosis of a variant form of chronic granulomatous disease (CGD) could be established in an 11-year-old girl who had been treated for atopic dermatitis for many years. In addition to severe superinfections of lesions of the skin, the following symptoms were found currently or in her history: an episode of chronic diarrhoea (suspected as lactose intolerance), an endomyocarditis, a paranephritic abscess and recurrent lymph node abscesses. This case is demonstrated to underline the importance of extensive immunologic diagnostics in situations of recurrent severe infections of the skin, especially if other organs are involved. Diagnosis and type of CGD were strongly indicated by flow cytometrical measurement of H2O2 and cytochrome b558-expression by neutrophils and confirmed by a Western blot test. No immunoreactive p47phox could be found in the patient's cells. In this autosomal recessive variant of CGD some retained ability of phagocytes to produce reactive oxygen intermediates was present. Special management of patients with CGD is necessary to prevent serious infectious complications. Genetic counselling is another important consequence of the correct diagnosis.

We have demonstrated that human fibroblasts can release O2-. radicals by an NADPH oxidase system that appears to be functionally similar to the phagocytic system. Further analysis of these systems, however, with respect to the low-potential b-type cytochromes involved suggests that these two O2-.-generating systems are not structurally identical. Immunoblot analysis of fibroblast membranes with six different antibodies directed against both subunits of human neutrophil cytochrome b-558 indicated that the b-type cytochrome molecules involved in these systems were not identical. None of these anti-(neutrophil cytochrome b) antibodies recognized a similar cytochrome in fibroblast membranes, suggesting that the two cytochrome species are immunologically distinct. In addition, fibroblasts obtained from a patient suffering from X-linked chronic granulomatous disease (CGD) had a normal cytochrome b-558 content compared with control fibroblast membranes, whereas the cytochrome b-558 concentration in polymorphonuclear leucocytes (PMNs) from this patient was decreased to 10% of that found in PMNs from healthy controls. Likewise, the stimulated O2-. release in PMNs from this patient was less than 10% of that in control PMNs, whereas the fibroblasts showed stimulated O2-.-release rates that were indistinguishable from those of fibroblasts obtained from healthy persons. Since the genetic mutation responsible for this type of CGD results in the absence of cytochrome b-558 in PMNs, fibroblasts should be affected in the same way if both cytochrome species were identical. These results suggest therefore that the low-potential b-type cytochromes in PMNs and fibroblasts are structurally and genetically distinct.