Association of adriamycin-induced resistance to NK-mediated lysis with sialic acid level and immunological reactivity of transferrin receptors and glycophorin A.
Adriamycin (ADM) can increase sialic acid content in K 562 cells and reduce their susceptibility to NK-mediated lysis. In this report, hypothetical relationship between this resistance and augmentation in sialylation has been investigated. Variations in the time of exposure to ADM showed that 12 hours were sufficient to cause maximal recruitment of benzidine-positive cells, growth inhibition and resistance to NK-mediated lysis. On the contrary, the membrane sialic acid density seemed stable and 24 hours of drug exposure were necessary to observe a clear rise in sialic acid. Neuraminidase treatment of control and ADM-treated K 562 cells was associated with an obvious enhancement in their susceptibility to NK-mediated lysis which can be explained by an increase in the target-effector binding ability as assessed by a direct conjugate-forming cell assay. However, the neuraminidase treatment did not modify the sensitivity difference to lysis between untreated and ADM-treated cells. As compared to control the reactivity of ADM-treated cells was higher with an antiglycophorin A (GPA) MAb and lower with an antitransferrin receptor (TFR) MAb. Kinetic studies suggested that GPA expression is a better index of ADM-induced resistance to NK-mediated lysis than TFR expression. In addition, neuraminidase treatment showed that TFR and GPA modulations induced by ADM can be correlated with sialylation alterations.
Benoist
H
H
Laboratoire de Physiologie Cellulaire, Faculté de Pharmacie, Reims, France.
Madoulet
C
C
Trentesaux
C
C
Carpentier
Y
Y
Joly
P
P
Jardillier
J C
JC
Desplaces
A
A
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D006021:Glycophorins / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D011990:Receptors, Transferrin / Q000276:immunology*; D012794:Sialic Acids / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000276:immunology*
D006021:Glycophorins; D011990:Receptors, Transferrin; D012794:Sialic Acids; D012795:Sialoglycoproteins; D004317:Doxorubicin; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid