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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 42 (1995), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The skin afferent lymph dendritic cell (DC) spontaneously forms clusters with autologous T cells. The role of adhesion molecules and cytokines in this process was investigated. Analysis of the expression of adhesion receptors on the canine peripheral lymph DC revealed the presence of CD54, CD58, CD18 as well as CD49d and CD49e molecules and cell surface fibronectin. The CD54 and CD58 molecules were found to play a key role in the ‘spontaneous’ lymph cell clustering. Antibody against fibronectin, a substrate for CD49d and CD49e receptors, reduced DC-lymphocyte binding. Analysis of the effect of cytokines revealed that the pro-inflammatory IL1β rather than ILlα, and TNFα may be responsible for the enhanced lymph cell in vitro clustering. The IL6 had no such augmenting effect. The enhancing effect of endogenous ILlβ present in lymph was reduced by the ILlβ neutralizing antibody. The effect of exogenously added ILlβ was also limited by the IL1 receptor antagonist. The ILlRa alone had no effect on cell binding, even when used in the high doses. Neutralizing of ILlRa in lymph with the specific antibody brought about augmented cluster formation. The enhancing properties of TNFα on cell binding were reduced by the TNFα neutralizing antibody. The IL10 significantly limited lymph DC cluster formation with T cells. In conclusion, these data demonstrate that the present in lymph IL1β and TNFα may be responsible for the observed in vitro enhanced cluster formation of lymph DC with autologous T lymphocytes. Cell binding can be reduced by ILlRa and by IL10. It provides insight into the potential clinical use of these inhibitors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 35 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To investigate the mechanism of spontaneous attachment of afferent lymph lymphocytes to dendritic cells, cells from canine skin lymph were used. There were 3.3 ± 2.8% of veiled cells in clusters found in lymph flowing from the cannulated lymph vessel. The number of clusters forming ex vivo in the collected lymph samples increased as a function of time and was temperature dependent. Incubation of cells with proteolytic enzymes or monosaccharides did not alter cell interactions. The ability of veiled cells to bind lymphocytes was independent of divalent cations but reduced by xylocaine and retinoic acid. Among steroids only methylprednisolone showed an inhibitory effect on cluster formation, Indomethacin and acetylsalicylic acid had no blocking activity on cell binding. Also, no effect was seen after treatment with cycosporine A and azathioprine. An enhanced cluster formation after desialation with neuraminidase was observed The desialated cells were cultured in order to study their stimulatory and accessory cell functions. No enhancement of autologous mixed leucocyte reaction was seen, but a significantly higher responsiveness to a suboptimal dose of phytohaemagglutinin was observed. The N-ase-mediated non-specific cell attachment could be abrogated by cell washing or treatment with EDTA or xylocaine.This study indicates that cluster formation by skin lymph veiled cells and lymphocytes is a spontaneous process which cannot be controlled by means usually effective in regulating the in vitro induced clustering of antigen-stimulated cells.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 179 (1981), S. 69-80 
    ISSN: 1433-8580
    Keywords: Immunosuppression ; Liver perfusate ; Ischemic damage ; Immunsuppression ; Leberperfusate ; ischämische Schädigung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Um die Freisetzung eines immunosuppressiven und zytotoxischen Faktors von ischämisch geschädigten Lebertransplantaten zu prüfen, wurden BDE- und DA-Ratten die Lebern entnommen. Nach einer sechsstündigen Aufbewahrung bei Raumtemperatur perfundierten wir intraportal ein- oder fünfmal mit 2 ml/g Ringerlösung. Der Proteingehalt betrug 0,9 oder 2,8–3,9 mg/ml. Wurde LEW-Ratten mit BDE-Nierentransplantaten 5 Tage lang vom Tag der Transplantation an 2 ml eines einmal perfundierten LP's verabreicht, überlebten die Tiere 8,9 ± 1,8 Tage signifikant länger (Kontrolle 6,5 ± 0,5 Tage), bei Injektion eines fünfmal perfundierten LP's 10,3 ± 1,3 Tage. Behandelten wir die Empfänger für 10 Tage mit dem fünffach perfundierten LP, erhöhte sich die Überlebensdauer auf 9–34 Tage, durchschnittlich auf 15,3 ± 7,3 Tage. Nieren, Milz und Herz wurden BDE-Ratten entnommen und bei Raumtemperatur 6 h lang aufbewahrt, Gewebeextrakte hergestellt, und der Proteingehalt mit Ringerlösung auf 3–4 mg/ml eingestellt. LP und Gewebeextrakte wurden einer MLC von LEW- und BDE-Zellen und einer LEW-Zell-Stimulation mit PHA zugegeben. Die LEW-Lymphozyten und die BDE-Fibroblasten inkubierten zusammen mit dem LP sowie den Gewebeextrakten 3 Tage lang. Die Blastogenese in der MLC- und der PHA-Stimulation wurde durch die LP's stark inhibiert, ebenso durch die Nieren, Herz und Milzextrakte, jedoch geringer als bei LP's. LP's verursachten starke Lymphozyto- und Fibroblastentoxizitäten, ebenso Nierenextrakte, Herz- und Milzextrakte aber weniger. Gut konservierte, nicht jedoch ischämisch geschädigte Nierenextrakte zeigten die gleiche Inhibition sowie Zytotoxizität wie eine ischämisch geschädigte Niere. Hitzeinaktivierung auf 70°C bewirkte eine leichte Verminderung der Inhibition und Zytotoxität. Der Organfaktor ist kein Zerfallsprodukt eines ischämisch geschädigten Gewebes, sondern ein normaler Bestandteil der Zellen, welcher insbesondere in der Leber vorhanden und relativ thermostabil ist.
    Notes: Summary These studies demonstrate the presence of an immunosuppressive and cytotoxic factor in the perfusate of ischemic damaged liver.A BDE rat liver perfusate (LP) was prepared after 6 h warm ischemia by intraportal perfusion with 2 ml/g of Ringer's solution (one time-LP1 or five times-LP5 with the same volume of solution). Protein amount of LP1 and LP5 was 0.9 and 2.8–3.9 mg/ml. In vivo activity of the hepatic perfusates was studied by effect on renal allograft survival time. LEW rats with BDE kidney transplant, treated daily with 2 ml of LP1 for 5 days, starting on the day of grafting, survived 8.9 ± 1.8 days, significantly longer than control animals (6.5 ± 0.5 days). After administration of LP5 renal recipients survived 10.3 ± 1.3 days and when the treatment with LP5 was prolonged to 10 days animals survived 9–34 days (mean 15.3 ± 7.3 days). The presence of the suppressive factor was also studied in renal, spleen and heart extracts, prepared after 6 h warm ischemia. Protein amount of extracts was adjusted to 3–4 mg/ml by Ringer's solution. Immunosuppressive activity of LP and other organ extracts was tested in vitro by their influence on MLC reaction (LEW and BDE lymphocytes) and on LEW cells in the PHA stimulation assay. Lymphocyte blastogenic response in MLC reaction and in culture with PHA was strongly inhibited by LP but weakly by organ extracts. Hepatic perfusates were cytotoxic against lymphocytes and fibroblasts in a three day cultures. Cytotoxic activity of the organ extracts was lower than LP. Extract of the cold preserved kidneys showed immunosuppressive and cytotoxic effect like extract of ischemically injured kidneys but smaller than LP. After heat inactivation at 70°C the activity of hepatic perfusate decreased. Immunosuppressive organ factor (IOF) seems to be a normal cell component, not a decomposition product of the ischemically damaged hepatic tissue.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 360 (1983), S. 17-27 
    ISSN: 1435-2451
    Keywords: Liver transplantation ; Hepatic immunosuppression ; Humoral transferfactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Um den Mechanismus der immunologischen Folgezustände nach Lebertransplantationen zu untersuchen, verpflanzten wir bei 58 LEW-Ratten orthotop Lebern von verschiedenen Inzuchtratten; dabei wurde das Transplantat durch ein hepaticoaortales Segment arterialisiert. Die Überlebensdauer war vom jeweiligen Spenderstamm abhängig, so überlebten bei LBNF 1-Lebern (n = 12) 67 %, bei WiS- (n = 20) 60 % und bei BUF-Transplantaten (n = 14) 43 % indefinitiv. Bei der DA- auf -LEW-Kombination (n = 12) zeigte kein Empfänger eine indefinitive Überlebensdauer. Leberperfusate (LP) von 10 BDE und 10 LEW wurden hergestellt, indem wir die Lebern nach Entnahme 6h bei Raumtemperatur aufbewahrten, danach via Vena portae mit 2ml/g Lebergewicht Ringlösung fünfmal cyclisch perfundierten. Nach Applikation von LP bei BDE-nierentransplantierten LEW überlebten die Tiere nach fünftägiger Behandlung 10,2 ± 1,3d (Kontrolle 6,5 ± 0,5d; P〈0,001) bei zehntägiger Behandlung 15,3 ± 7,3 d. In vitro inhibierte LP die PHA-Stimulation von LEW-Lymphoidzellen zu mehr als 90 %, die Con A-Stimulation von LEW-Milzzellen zu mehr als 95 %. Im MLC supprimierte LP ebenfalls die Stimulation zu mehr als 97 % bei verschiedener Kombination von Stimulating- und Responding-Zellen. Unseres Erachtens wird der unspezifische immunosuppressive Leberfaktor aus ischämisch geschädigten Transplantaten freigesetzt, und somit die Abstoßung in der Induktionsphase verhindert. Bei den mehr als 4 Monate überlebenden WiS-Leberempfängern wurde die Milz entnommen und die GvHR getestet. Alle Tests ergaben einen Reaktionsgrad III. Spezifische Hauttransplantate bei den gleichen Empfängern überlebten idefinitiv, unspezifische Haut (DA) wurde jedoch regelrecht abgestoßen (7,6 ± 0,5 d). Somit ist die celluläre Immunität intakt, gleichzeitig aber die Immunantwort gegen spezifische Antigene abgeschwächt. Durch Serumtransfer von mehr als 6 Monate überlebenden WiS-Leberempfängern konnten WiS-Nierenempfänger verlängert überleben (20,7 ± 3,4d, Kontrolle 6,2 ± 1,0 d;P 〈 0,001). Der Transfer von Lymphoidzellen (1 × 108) der Leberempfänger zeigte keine significante Immunosuppression (Nierenempfänger überlebten nur 8,0 ± 2,0d). In der Erhaltungsphase scheinen somit humorale transferierbare immunosuppressive Agentien für die Aufrechterhaltung der Lebertransplantatfunktion entscheidend zu sein.
    Notes: Summary To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialisation of the grafts was achieved with an hepaticoaortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67 % (n = 12), WiS- in 60 % (n = 20) and BUF- in 43 % (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 ± 1.3 d (control: 6.5 ± 0.5 d;P 〈 0.001), at 10 days treatment 15.3 ± 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90 % and the ConA-stimulation of LEW spleen cells in more than 95 %. In MLC LP showed strong inhibitory effect (inhibition rate 〉 97 %) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 ± 0.5 d). We therefore can conclude that the cellular immunsurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (〉 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 ± 3.4d, control 6.2 ± 1.0 d;P 〈 0.001). Lymphoid cell transfer (1 × 108) did not result in significant prolongation of survival time (8.0 ± 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.
    Type of Medium: Electronic Resource
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