Regulatory factors produced by lymphocytes. I. The occurrence of multiple alpha-lymphotoxins associated with ribonuclease activity.
Supernatant fluids of mitogen-activated human tonsil lymphocytes contain large amounts of a factor toxic to mouse L cells. This substance, with a m.w. of 80,000 +/- 5,000 daltons, is called alpha-lymphotoxin (alpha-LT), to differentiate it from another toxin elaborated by mitogen activated human blood lymphocytes, called beta-lymphotoxin (beta-LT), which differs from alpha-LT in size (45,000 +/- 5,000 daltons), antigenicity, and stability. Further purification of alpha-LT by sequential phosphocellulose and DEAE-cellulose chromatography and polyacrylamide gel electrophoresis (PAGE) identifies a series of cytotoxins differing in ion exchange characteristics and electrophoretic mobilities. The three PAGE fractions (PAGE Ia, Ib and II), recovered in 2, 4.6, and 21% yield from the starting serum-free culture supernatant, represent purifications of 24-, 24- and 1851-fold, respectively. Each cytotoxic fraction has a ribonuclease activity. Comparison of RNase and mouse L cell cytotoxic activities of the three alpha-LT fractions shows that both activities for all three fractions have a similar temperature stability pattern and that both are similarly inhibited by DNA, single strand forms better than double strands, by glycerol in 5 to 20% concentration, and by protein denaturing reagents. These observations suggest, but do not prove, that mouse L cell toxicity and RNase activity are mediated by the same substance, which appears to occur in multiple or isozymic forms.
D000818:Animals; D002474:Cell-Free System; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000494:pharmacology; D006801:Humans; D007739:L Cells / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000032:analysis* / Q000302:isolation & purification; D051379:Mice; D014066:Palatine Tonsil / Q000276:immunology; D012260:Ribonucleases / Q000032:analysis*; D013696:Temperature
D008233:Lymphotoxin-alpha; D004247:DNA; D012260:Ribonucleases