Characteristics of soluble tumour-derived proteins that inhibit natural killer activity.
We have previously shown that various benign and malignant natural killer (NK)-resistant monolayer cells inhibit endogenous human NK activity, probably by reducing the secretion of cytotoxic factors from the effector cells. The nature of the molecules responsible for the inhibition has been unclear. In this study we show that phosphate-buffered saline (PBS) extracts of ovarian cystadenocarcinoma tissue and normal uterine smooth muscle strongly inhibit NK activity. Fractionation of tumour extracts by gel chromatography revealed major inhibitory activity in the Mr range 160,000-180,000, and other weaker inhibiting activities in the Mr ranges 50,000-70,000 and 20,000. The active material of Mr range 160,000-180,000 was adsorbed on anion exchange chromatography column at neutral pH and physiologic NaCl concentration, and it was eluted by 0.31-0.34 M NaCl. The inhibitory molecule was sensitive to proteolysis. No relation of this compound to immunoglobulins or trypsin and urokinase inhibitors was detected. The unfractionated extract inhibited NK activity apparently by the same mechanism as the monolayer target cells, i.e. by reducing the secretory capacity of effector cells. The data strongly suggest that the NK-inhibiting compounds described in this work are involved in the inactivation of NK cells by intact monolayer cells.
D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D010450:Endopeptidases; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D055646:Killer Factors, Yeast; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000276:immunology; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D055646:Killer Factors, Yeast; D009363:Neoplasm Proteins; D011506:Proteins; D014361:Trypsin Inhibitors; D010450:Endopeptidases