THE PUTATIVE ROLE OF ARYLSULFATASE IN INTERLEUKIN-2-MEDIATED CYTOTOXICITY AND INTERLEUKIN-7-MEDIATED BACTERICIDAL ACTIVITY OF NATURAL-KILLER-CELLS

We have examined the cytolytic and bactericidal activity of resting an d cytokine-stimulated natural-killer (NK) cells against K562 and Daudi cell lines and Escherichia coli, respectively. Unstimulated NK cells showed considerable cytolytic activity against K562 (64 +/- 4%) and re latively low activity against the Daudi cell lines (22 +/- 9%). Pretre atment of NK cells with the arylsulfatase (AS) type-II-specific inhibi tor NaH2PO4 reduced cytotoxicity towards K562 and Daudi 1.3- and 2.9-f old (p < 0.05; n = 12), respectively, indicating that AS participates in NK-mediated cytotoxicity. Interleukin-2 (IL-2) (200 units/ml) cause d a 1.3- and 3.5-fold (p < 0.5; n = 12) enhancement of NK cytotoxic ac tivity against K562 and Daudi, respectively. Pretreatment of these cel ls with the AS type-II-specific inhibitor NaH2PO4 reduced cytotoxicity 1.1-fold towards K562 (p > 0.05; n = 12) and 1.2-fold towards Daudi ( p > 0.05; n = 12) indicating that AS does not participate in IL-2-medi ated NK cytolytic activity against these cell lines. IL-7 (3 units/ml) did not cause any enhancement of NK cytolytic activity. Unstimulated NK cells showed considerable bactericidal activity against E. coli (23 +/- 4%). Incubation of resting NK cells with NaH2PO4 reduced the bact ericidal effect only by 1.09-fold (p > 0.05; n = 12), indicating that AS does not mediate this effect. IL-2 (200 units/ml) and IL-7 (3 units /ml) enhanced the bactericidal activity 1.5- and 2.2-fold, respectivel y (p < 0.05; n = 12). This effect was not influenced by incubation of IL-2-stimulated cells with NaH2PO4, indicating that AS does not partic ipate in the IL-2-mediated NK bactericidal effect. IL-2 seems to exert its stimulatory effect upon NK-mediated bactericidal activity by a di fferent, non-AS-dependent mechanism. However, incubation of IL-7-stimu lated NK cells with NaH2PO4 reduced the NK bactericidal effect by 1.2- fold (p < 0.05; n = 12), indicating that AS may have a role in this re action. These data can be further confirmed by detection of AS through degranulation of NK cells, showing that IL-2 induced only mild degran ulation of resting and f-MLP-stimulated NK cells (26 +/- 1% vs 22 +/- 2% and 31 +/- 2% vs 29 +/- 2, respectively) (p > 0.05; n = 8). In cont rast, IL-7 showed significant enhancement of AS release in resting or f-MLP-induced NK cells (36 +/- 3% vs 22 +/- 2% and 49 +/- 3% vs 29 +/- 2%, respectively) (p < 0.05; n = 8).