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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The surface characteristics of the mouse spleen cells mediating antibody-dependent cytotoxicity (ADCC) against antigen-coated chicken erythrocytes have been studied by several different column fractionation methods The major effector cells in this system were shown to be surface-adherent and could be depleted from spleen cells by passage through glass-bead ovalbumin/anti-OA immune complex columns (Fc receptor-binding), glass-bead immunoglobulin/anti-mouse Ig columns (Fc receptor and surface immunoglobulin-binding), and glass-bead mouse Ig/rabbit (Fab')2-anti-mouse Ig or Sephadex G-200/rabbit anti-mouse Ig columns (surface immunoglobulin binding) The concentration of EDTA in the medium used to fractionate the cells played a significant role in determining whether surface immunoglobulin could be demonstrated on the ADCC effector cells. From these results, the conclusion was drawn that ADCC on the part of mouse spleen cells could be mediated by surface-adherent, Fc receptor-positive cells bearing surface immunoglobulin of unknown origin. The possibility that ADCC can be mediated by a heterogenous population of cells in the mouse spleen is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2592
    Keywords: Chemotherapy ; ovarian carcinoma ; natural killer cells ; interleukin-2 ; lymphokine-activated killer cells ; multidrug resistance ; P-glycoprotein ; immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The sensitivity of tumor cells to lysis by natural killer (NK) and interleukin-2 (IL-2)-activated killer (LAK) cells was studied in three ovarian carcinoma cell lines (2780.9S, SKOV-3, and CHOAUXB1), four multidrug-resistant (MDR) variants, and a melphalan-resistant line. The antitumor activity of LAK cells was evaluated both by51Cr release and by conjugate formation assays. Four of four P-glycoprotein-positive (P-gp+) MDR ovarian carcinoma cell line variants were lysed by human LAK cells to a greater extent than were their drug-sensitive counterparts. In contrast, a melphalan-resistant ovarian carcinoma cell line that does not overexpress P-gp (P-gp−) did not exhibit an increased susceptibility to LAK cells relative to its parental cell line. Two of the four P-gp+ MDR ovarian carcinoma cell line variants were tested for human NK cell susceptibility and this was found to be unchanged or decreased. The P-gp+ MDR ovarian carcinoma cell line 2780.AD645 showed a higher frequency of tumor cell binding to LAK cells than did the drug-sensitive parental line. A monoclonal antibody (mAb) against a cell surface epitope of P-gp, MRK16, used at 1 μg/ml, enhanced the LAK susceptibility of P-gp+ MDR ovarian carcinoma cell lines. However, when incubation with 10 μg/ml MRK-16 antibody (Ab) was followed by 12.5 μg/ml F(ab′)2 goat anti-mouse (GAM) immunoglobulin (Ig), the increased LAK susceptibility of P-gp+ MDR cell lines was inhibited. These data strongly suggest that P-glycoprotein-positive MDR ovarian carcinoma cells not only are targets for LAK cells, but are more sensitive than their drug-sensitive parental lines. This is in contrast to their susceptibility to NK cells, which is low to start with and remains unchanged or even decreased in MDR cells. It is postulated here that P-gp or associated changes result in a greater frequency of effector-target cell binding, leading to increased LAK cell cytotoxicity.
    Type of Medium: Electronic Resource
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