title: Non-granular proteolytic enzymes of rat interleukin-2-activated natural killer cells. III. Enhancement of A-NKP 1, 2, and 3 proteolytic activities (cleaving after Arg, Phe and Pro) in response to interleukin-2.
abstract: Rat IL-2-activated natural killer (A-NK) cells contain a number of cytosolic proteases (A-NKP 1-3), two of which (A-NKP 2 and A-NKP 3) have been implicated in cytolytic function. The 3.2.3 monoclonal antibody directed against the NKRP-1 signal transduction molecule, a selective marker of rat NK cells, was used to select a highly purified population of rat NK cells. When the 3.2.3-positive cells were cultured in the presence of IL-2, a time-dependent increase in the specific activity of A-NKP 1, A-NKP 2 and A-NKP 3 was observed which paralleled the observed increase in lytic activity against both NK-sensitive (YAC-1) and NK-resistant (P815) targets. A transient rise was observed in the specific activity of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase (BLT esterase, i.e. granzyme A). These results lend further support to the hypothesis that A-NKP 2, a component of the rat A-NK cell multicatalytic proteinase complex/proteasome, and A-NKP 3 contribute to the cytolytic function of A-NK cells. Moreover, these results further suggest that proteolytic enzymes that contribute to cell-mediated cytotoxicity are not restricted to the granzymes or localized only in the lytic granules of effector cells.
authors.affiliation: University of Pittsburgh Cancer Institute, PA 15213, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Kitson
authors.forename: C A
authors.initials: CA
authors.lastname: Miller
authors.forename: R H
authors.initials: RH
authors.lastname: Goldfarb
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D010450:Endopeptidases / Q000032:analysis* / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007376:Interleukin-2; D010450:Endopeptidases