Phospholipase A2 activity and calpactin I levels in rat lymphokine-activated killer cells: Correlation with the cytotoxic activity

In the present paper we have shown evidence for a significant increase of type II sPLA₂ activity in A-LAK cells. The A-LAX-mediated cytotoxicity against YAC-1 target cells was strongly inhibited by two inhibitors of sPLA₂, p-BPB and mepacrine, suggesting the involvement of this enzyme in the lytic mechanism of A-LAK. On the other hand, stimuli such as A23187 ionophore and TPA, which were able to induce in control cells an increased AA release, failed to cause this effect in IL-2-treated cells, suggesting that PLA₂ was not active in these cells. Thus, we analyzed the levels of calpactin I, which is considered to be involved in the down-regulation of PLA₂ activity. HrIL-2 treatment led to an increased expression of calpactin I at both the RNA and the protein level. A substantial portion of calpactin I was associated with the external surface of A-LAK and was able to exert a strong inhibitory effect on a purified porcine pancreatic PLA₂ activity in vitro. Our results suggest that the role of calpactin I could be relevant to regulate PLA₂ activity, and to protect the effector cells against a possible toxic effect which this enzyme could exert if present at high levels.