BLT-esterase activity following in vitro and in vivo activation of human lymphocytes with interleukin-2. In vivo IL-2 induces BLT-esterase.
BLT-esterase and cytolytic activity by human in vitro and in vivo generated Lymphokine Activated Killer (LAK) cells were measured. Lysates made from peripheral blood lymphocytes (PBL) of both normal donors and cancer patients receiving IL-2 therapy were assayed for BLT-esterase activity in a spectro-photometric assay. Cytotoxicity of PBL was measured in a 51Cr-release assay. Both BLT-esterase activity and cytotoxicity increased when normal-donor PBL were stimulated in vitro with IL-2, with greater activities at higher IL-2 concentrations. The activities also increased over time, peaking at 6 days of in vitro stimulation. Patient PBL had increased BLT-esterase and cytotoxic activities after 4 weeks of in vivo IL-2 treatment. This association of BLT-esterase activity and cytotoxicity with IL-2 activation is consistent with the model that LAK cytotoxicity is mediated by secretion of BLT-esterase associated cytolytic granules. Lymphocytes obtained after in vivo IL-2 treatment and cultured for 3-4 hours in IL-2 show markedly augmented cytotoxic activity but no increase in their BLT-esterase activity. These results indicate that the increased cytotoxicity observed after this brief pulse of in vitro IL-2 following in vivo IL-2 treatment must result from effects of IL-2 other than the production of more esterase-containing cytolytic granules.
Cannon
A
A
Department of Human Oncology, University of Wisconsin, Madison.
Hank
J A
JA
Sondel
P M
PM
D002470:Cell Survival / Q000187:drug effects; D015925:Cryopreservation; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis*
D007376:Interleukin-2; D011994:Recombinant Proteins; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human