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  • Cytolysis  (2)
  • Interleukin-1 (IL-1)  (1)
  • 1
    ISSN: 1432-0851
    Schlagwort(e): Cyclophosphamide ; IL-2, NK activity ; Cytolysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL-2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days −10 and −15 followed by IL-2 (50 000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day −10 or −15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoGM1, prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0851
    Schlagwort(e): Neuroblastoma ; Cytolysis ; ICAM-1 ; ICAM-2 ; Tumorigenicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-genetransduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF=3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1+) (CMF=64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1+ was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 100∶1) compared to neuro-2a/LN (48.6%) (P〈0.001). Blocking of neuro-2a/LN and neuro-2a/ICAM-1+ lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1+ cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1+ lines expressed ICAM-2 (MCF=16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-1-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1+ transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity; mice inoculated with neuro-2a/ICAM-1+ cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P〈0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastome with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorgenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1573-2592
    Schlagwort(e): Interleukin-1 (IL-1) ; IL-6 ; bone marrow transplantation ; lymphoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We evaluated the cytolytic function, phenotypic characteristics, and cytokine levels of 22 patients with non-Hodgkin's lymphoma and 7 with Hodgkin's disease receiving interleukin-la (IL-1α) following autologous bone marrow or peripheral blood stem cell transplantation. IL-1α was given i.v. over 6 hr, between day 0 and day +13 posttransplant. On day +14, cells from patients receiving high-dose IL-1α (3.0 μg/m2/day) had significantly enhanced killing of natural killer (NK)-sensitive and -resistant lymphoma targets compared to those treated with low-dose IL-1α (0.1, 0.3, or 1.0 μg/m2/day). The differences in cytolytic function between the two groups persisted but were not as striking on day +28. Patients receiving higher-dose IL-1α had a significantly increased proportion of CD3+ T cells on days +14 and +28, while the proportion of CD16+ and CD56+ NK cells was decreased compared to those of patients treated with the lower dose. There were no detectable levels of IL-2, interferon-γ, or tumor necrosis factor-α in the plasma of patients receiving IL-1α posttransplant. However, higher-dose IL-1α therapy was associated with significant increases in serum IL-6 levels in comparison to those in patients receiving low-dose IL-1α. IL-1α may increase cytolytic function post-bone marrow transplantation; it remains to be determined, however, whether this would have an impact on decreasing relapse rates of patients undergoing transplantation for lymphoma.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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