RNK granule extract cytolysis: increased tumor susceptibility and release of proteochondroitin sulphate inhibitor in high NaCl.
The insensitivity of the natural killer (NK)-resistant L5178Y-F9 murine T-cell lymphoma to granule extracts from a rat NK leukemia could be preferentially reversed in increased NaCl (0.25 M) compared with the NK- and granule extract-sensitive SL2-5. The high salt effect predominated in the binding rather than the lytic phase of the extract reaction similar to the activity of extract inhibitory supernates preferentially produced from L5178Y-F9 cells. Exposure of the L5178Y-F9 to 0.25 M NaCl was associated with an increased production of inhibitory supernate and an increased sensitivity of the cell as an extract target. Pretreatment of inhibitor-containing supernatant or inhibitor-producing L5178Y-F9 cells with pronase or chondroitinase AC reduced the inhibitory activity of the resultant supernates, and L5178Y-F9 supernates treated with anti-chondroitin sulphate AC antibodies exhibited reduced inhibitory activity. These observations and the previously reported molecular weight heterogeneity and protease sensitivity of the inhibitor argue that chondroitin sulphate AC-containing proteoglycans released from the tumor cell surface may inhibit cytolysin activity, contributing to the preferential resistance of the L5178Y-F9 to rat NK granule extract cytolysis.
Chow
D A
DA
Immunology Department, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000037:antagonists & inhibitors*; D002810:Chondroitinases and Chondroitin Lyases / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D003603:Cytotoxins / Q000633:toxicity*; D010450:Endopeptidases / Q000494:pharmacology; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D012965:Sodium Chloride / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011508:Chondroitin Sulfate Proteoglycans; D003603:Cytotoxins; D012965:Sodium Chloride; D010450:Endopeptidases; D002810:Chondroitinases and Chondroitin Lyases