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-LAK-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.
Cifone
M G
MG
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
Cironi
L
L
Roncaioli
P
P
Martinotti
S
S
Toniato
E
E
Cilenti
L
L
Botti
D
D
Solito
R
R
Parente
L
L
Santoni
A
A
D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D008213:Lymphocyte Activation; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology; D013552:Swine
D017306:Annexin A2; D007376:Interleukin-2; D012333:RNA, Messenger; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2