Human Granulocyte-Macrophage Colony Stimulating Factor: An Effective Direct Activator of Human Polymorphonuclear Neutrophilic Granulocytes

Granulocyet-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated. For detection of granulocyte activation the following assay systems were used: 1) lucigenin-dependent chemiluminescence (CL),2) superoxide-dismutase (SOD) inhibitable cytochrome C-reduction (superoxide),3) horseradish peroxidase-mediated oxidation of phenol red (hydrogen peroxide),4) release of myeloperoxidase, 5) ultrastructural detection of hydrogen peroxide-production, and 6) scanning and transmission electron microscopy (SEM and TEM, respectively). A significant CL response was seen upon stimulation with recombinant human GM-CSF at concentrations ranging from 1 to 103 U/ml. The CL response started within 5-10 min with a maximum at 60 – 90 min and lasted more than 3 h. Thereafter granulocytes were completely deactivated to restimulation with the same mediator and with Tumor Necrosis Factor, but respondend to other triggers of the oxidative burst, whereas the response to f-met-leu-phe was significantly increased, The CL signal was completely blocked by an antiserum to GM-CSF. Moreover, the response was significantly inhibited by SOD and D-mannitol, suggesting the involvement of distinct reactive oxygen species (ROS) in generating the CL response. Significant amounts of superoxide were detected within 180 min after stimulation with GM-CSF, whereas, release of hydrogen peroxide and peroxidase were only minimal as shown by functional and ultrastructural assays. Activation of granulocytes could be visualized by SEM and TEM. GM-CSF stimulated cells showed an increased adherence to the substratum developing polarized filopodia and an increased number of intercellular vesicles within 30 min after addition of the stimulus. The results clearly demonstrate that GM-CSF directly stimulates granulocytes and, particularly, their oxidative metabolism. Therefore, GM-CSF which is probably released by epidermal cells appears to be a candidate for neutrophil activation in the skin, and thereby may play a crucial role in inflammatory skin diseases

Onlinegestützte Audience Response Systeme: Förderung der kognitiven Aktivierung in Vorlesungen und Eröffnung neuer Evaluationsperspektiven

Audience Response Systeme bzw. Clicker bieten die Möglichkeit, Studierende aktiv in Lehrveranstaltungen einzubinden, indem ihnen auf Smartphones oder eigens dafür vorgesehenen Geräten Fragen zur Verfügung gestellt werden (z.B. SMILE]). Das Abstimmungsergebnis kann wiederum vom Dozierenden aufgegriffen und in der Veranstaltung thematisiert werden. Das an der Technischen Universität Dresden entwickelte System „Auditorium Mobile Classroom Service“ (AMCS) bietet zahlreiche weitere Funktionalitäten, die es erlauben Studierende bei Lernprozessen in der Vorlesung zu unterstützen und gleichzeitig eine informative Evaluation der Lehrveranstaltung ermöglichen. Die Funktionalitäten des Systems wurden auf der Grundlage lernpsychologischer Forschung entwickelt (bspw. Modellen des Selbstregulierten Lernens): sie haben gemeinsam das Ziel, Studierende in Abhängigkeit individueller Bedürfnisse dabei zu unterstützen, in der Vorlesung möglichst viel zu lernen. Die Lehrenden haben darüberhinaus die Möglichkeit, umfangreiche Informationen zur Evaluation der Lehrveranstaltung zu gewinnen

Decreased Production of Interferon in Whole Blood Cultures Derived from Patients With Psoriasis

Patients suffering from psoriasis show many alterations with respect to their immune system as documented by in vitro test systems. In the present study we investigated the in vitro production of interferons (IFN) of leukocytes from psoriatic patients to stimulation with a variety of IFN inducers. Furthermore, the lymphoproliferative responses were tested. Whole blood cultures of 30 psoriatic patients showing moderate to severe disease activity and 21 cultures from healthy controls were stimulated with the mitogens PHA, ConA, and PWM, with PPD and Tetanus Antigen as IFN γ inducers and with C. parvum, PolyI-PolyC, and Herpes simplex virus as inducers of IFN α. Interferon activity was tested in the supernatant of 48-h cultures by using an antiviral assay. Lympho-proliferation was assayed in 5-d cultures in parallel. Psoriatic patients showed a significantly decreased IFN production to all the stimuli tested. There were no significant differences in the lymphoproliferative responses; only the response to PWM was slightly decreased. The decreased IFN production by leukocytes from psoriatic patients seems to be very remarkable since increased susceptibility to infections is not generally known in these patients

55-kd Tumor Necrosis Factor Receptor Is Expressed by Human Keratinocytes and Plays a Pivotal Role in Regulation of Human Keratinocyte ICAM-1 Expression

Tumor necrosis factor α (TNFα) is a potent modulator of human keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression. TNFα is known to exert its biologic effects by binding to specific cell-surface receptors. Two distinct TNF binding molecules, the 55-kd and the 75-kd TNF receptor (TNFR) recently have been found to be expressed by human cells. These two receptor types are independently regulated and differ markedly in their intracellular regions, indicating functional dichotomy. In order to gain further insight into the mechanisms underlying ICAM-1 regulation in human keratinocytes, in the present study, the receptor molecules mediating TNFα induced ICAM-1 upregulation in human keratinocytes was defined. Human keratinocyte TNFR expression was assessed using monoclonal antibodies that specifically recognize the 55-kd or the 75-kd TNFR. Using FACS analysis, normal (HNK) as well as transformed (KB) human keratinocytes were found to react with anti-55-kd TNFR, but not anti-75-kd TNFR antibodies. These immunofluorescence data were confirmed by Northern blot analysis revealing clearly detectable amounts of mRNA specific for the 55-kd TNFR in KB cells. Incubation of human keratinocytes with anti-55-kd TNFR antibodies at 37°C for 24h increased ICAM-1 expression in a TNFα-like fashion. Moreover, the well known synergistic effect of IFNγ plus TNFα on keratinocyte ICAM-1 induction could be mimicked by stimulation of cells with IFNγ plus anti-55-kd TNFR antibodies. Synergistic ICAM-1 induction was not associated with increased expression of the 55-kd TNFR in IFNγ-stimulated human keratinocytes. These studies indicate that human keratinocytes express the 55-kd TNF receptor and that this surface molecule may play an important role in regulation of human keratinocyte ICAM-1 expression

Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020.

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU

Дослідження структури порушених відкритою розробкою земель й пошук шляхів вдосконалення рекультивації залишкових виробок кар'єрів

Стаття присвячена дослідженням структури порушених земель, на ділянках з видобутку корисних копалин відкритим способом. Наведено площі порушень земель при розробці основних видів корисних копалин. Проаналізовано ризики, що виникають із несвоєчасною рекультивацією земель гірничого відводу, а також від покинутих гірничих виробок старих кар'єрів. Паралельно розглянуті обсяги відходів гірничого виробництва та їх повторне використання в якості заповнювача для залишкових вироблених просторів кар'єрів.The article is devoted to the research of land violation indicators at the extraction of minerals by surface mining method. Data gives about the land violations area at the mining key minerals. Ana-lyzed the risks from the not-on-time reclamation of the mining clam and abandoned excavations of the old quarries. In parallel considered the volumes of mining wastes and their reuse as aggregate for filling residual spaces of surface mines.Статья посвящена исследованиям площадей нарушения земель, связанных с добычей полезных ископаемых открытым способом. Приведены площади нарушений земель при разработке основных видов полезных ископаемых. Проанализированы риски, представляемые несвоевременной рекультивацией земель горного отвода, а также заброшенными горными выработками старых карьеров. Параллельно рассмотрены объемы отходов горного производства и их повторное использование в качестве заполнителя для остаточных выработанных пространств карьеров