CANCER-CELLS ISOLATED FROM MALIGNANT PLEURAL AND PERITONEAL EFFUSIONSINHIBIT PHOSPHOLIPASE A(2) ACTIVITY IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES

We studied the influence of cancer cells on the LTB4 production by hum an polymorphonuclear leukocytes (PMN). The cancer cells were isolated from malignant pleural effusion specimens taken from two patients or f rom a peritoneal effusion specimen of one patient. While human PMN pro duced LTB4 following stimulation with A23187, the addition of cancer c ells inhibited LTB4, 5-HETE and 12-HETE production by PMN in a cell nu mber-dependent manner, while the cancer cell lines also showed a simil ar inhibition. The addition of lysate of the breast cancer cells also inhibited in a dose-dependent manner the production of LTB4 by PMN fol lowing stimulation with A23187. The addition of arachidonic acid compl etely reversed the inhibition of PMN-LTB4 production by the addition o f the breast cancer cell lysates, thus suggesting inhibition at the ph ospholipase A(2) level. The addition of this lysate to the partially p urified human cytosolic PLA(2) also inhibited the PLA(2) activity. In contrast, the addition of lymphoma cells isolated from metastatic lymp hnodes did not inhibit the LTB, production from PMN. Since LTB4 is one of the important chemotactic factors for PMN and monocytes, these fin dings suggest that the inhibition of the PLA(2) activity by the cancer cells thus results in a reduced production of LTB, from PMN and contr ibutes to a predisposition to develop severe infection in patients wit h advanced cancer. (C) 1997 Elsevier Science Ireland Ltd.