Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Language: English
    In: Immunobiology, 2011, Vol.216(3), pp.334-342
    Description: Posttrauma apoptosis resistance of neutrophils (PMN) is related to overshooting immune responses, systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Recently, we have shown that the apoptosis resistance in circulating PMN from severely injured patients which is known to be mediated by high serum levels of pro-inflammatory cytokines can be overcome by the activation of Fas death receptor. Here, we aimed to study whether stimulation of surface Fas leads to the inactivation of hyperactivated PMN from critically ill patients with SIRS. PMN from 23 multiple trauma patients (mean injury severity score (ISS) 34 ± 1.9) were isolated at day 1 after admission to the trauma center. PMN from 17 volunteer blood donors served as controls. Neutrophil activity has been determined after short (1 h) and long-term (4 h) stimulation of freshly isolated PMN with immobilized agonistic anti-Fas antibodies. We found neutrophil chemotactic migration in response to IL-8, phagocytosis and oxidative burst to be significantly inhibited in control cells already after short-term (1 h) Fas stimulation. In contrast, inactivation of trauma PMN by agonistic anti-Fas antibodies was found to be efficient only after long-term (4 h) incubation of cells with agonistic antibodies. Thus, in trauma PMN down-regulation of neutrophil activity seems to be delayed when compared to cells isolated from healthy controls, suggesting impaired susceptibility for Fas stimulation in these cells. Interestingly, whereas Fas-mediated inhibition of phagocytosis and oxidative burst could be prevented by the broad range caspase inhibitor t-butoxycarbonyl-aspartyl(O-methyl)-fluoromethyl ketone (BocD-fmk), the chemotactic activity in response to IL-8 was unaffected. In conclusion, we demonstrate that stimulation of neutrophil Fas does not only initiate apoptosis but also induces inhibition of neutrophil functions, partially by non-apoptotic signaling.
    Keywords: Caspases ; Chemotaxis ; Neutrophils ; Oxidative Burst ; Phagocytosis ; Sirs ; Biology
    ISSN: 0171-2985
    E-ISSN: 1878-3279
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Immunobiology, 1994, Vol.191(1), pp.38-51
    Description: Cytokine-induced expression of adhesion molecules on leukocytes and endothelial cells (EC) is a crucial point in the process of organ transplant rejection. It has been shown that protein kinase C (PKC) is involved in this activation process. Verapamil and other calcium channel blockers seem to possess immunosuppressive qualities and ; some authors suggested that this is due to PKC- or calmodulin-antagonism. Thus our objectives were to further investigate the second-messenger systems involved in the stimulation of EC and to analyze whether the beneficial influence of calcium channel blockers on the outcome of transplantation is due to impaired expression of adhesion molecules on EC.. Our results, obtained in an model using human umbilical vein EC, show that IL-1-induced expression of intercellular adhesion molecule-1 (ICAM-1) is in part mediated by PKC and that parallel activation of calmodulin is required. Expression of ICAM-1 was reduced to 38.5% by PKC-inhibitor H7 and to 77.2% by calmodulininhibitor W7. In addition, data on the intracellular events in TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) is presented, showing that both PKC and, to a higher extent, calmodulin, are involved in this process. Expression of VCAM-1 was reduced to 63.7% by H7 and to 27.7% by W7. IL-1-induced expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) is PKC-dependent but insensitive to blocking of calmodulin. Though activation of adhesion molecule expression utilizes PKC and/or calmodulin as second-messenger pathways the investigated calcium channel blockers verapamil (R- and S-enantiomers), diltiazem and Ro 40-5967 failed to inhibit adhesion molecule expression.Surprisingly, higher concentrations of verapamil (〉 12.5 μ/ml) or Ro 40-5967 (5 μg/ml) significantly enhanced IL-1-induced expression of ELAM-1. ICAM-1-expression was also enhanced by verapamil, but not by Ro 40-5967 or diltiazem. This enhancement was only seen if verapamil was added maximally one hour after the cytokine stimulus indicating that transcriptional modulation is responsible for the observed effects. Our findings indicate that calcium channel blockers have an immunomodulating effect independent of adhesion molecule expression.
    Keywords: Biology
    ISSN: 0171-2985
    E-ISSN: 1878-3279
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Immunobiology, 2000, Vol.201(3), pp.332-346
    Description: CDS-positive cytotoxic T cells (CTL) recognize antigenic peptides in combination with major histocompatibility complex (MHC) class I molecules on the surface of syngeneic antigen presenting cells (APC). In the present paper we show that cells from tumor antigen-specific CTL clones present their cognate antigenic peptide to other CTL from the same clone. Inter-CTL peptide presentation resulted in activation of the cells of one CTL clone to MHC-unrestricted lysis of bystander cells. In contrast to the behaviour of this clone, another CTL clone did not lyse bystander cells after incubation with the cognate peptide, but was activated to self-destruction. The human herpes virus Epstein-Barr virus is involved in the pathogenesis of a broad spectrum of human neoplasias. Using freshly established non-clonal T cells with specificity for a peptide derived from an Epstein-Barr virus encoded antigen we found again lysis of MHC mismatched bystander cells as a consequence of inter-CTL peptide presentation, indicating that bystander lysis following antigen self-presentation is not a phenomenon restricted to long-term cultured T cell clones. The potential implications for immunosurveillance against cancer and for tumor escape mechanisms are discussed.
    Keywords: Biology
    ISSN: 0171-2985
    E-ISSN: 1878-3279
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages