Cancer cells isolated from malignant pleural and peritoneal effusions inhibit phospholipase A2 activity in human polymorphonuclear leukocytes

We studied the influence of cancer cells on the LTB4 production by human polymorphonuclear leukocytes (PMN). The cancer cells were isolated from malignant pleural effusion specimens taken from two patients or from a peritoneal effusion specimen of one patient. While human PMN produced LTB4 following stimulation with A23187, the addition of cancer cells inhibited LTB4, 5-HETE and 12-HETE production by PMN in a cell number-dependent manner, while the cancer cell lines also showed a similar inhibition. The addition of lysate of the breast cancer cells also inhibited in a dose-dependent manner the production of LTB4 by PMN following stimulation with A23187. The addition of arachidonic acid completely reversed the inhibition of PMN-LTB4 production by the addition of the breast cancer cell lysates, thus suggesting inhibition at the phospholipase A2 level. The addition of this lysate to the partially purified human cytosolic PLA2 also inhibited the PLA2 activity. In contrast, the addition of lymphoma cells isolated from metastatic lymphnodes did not inhibit the LTB4 production from PMN. Since LTB4 is one of the important chemotactic factors for PMN and monocytes, these findings suggest that the inhibition of the PLA2 activity by the cancer cells thus results in a reduced production of LTB4 from PMN and contributes to a predisposition to develop severe infection in patients with advanced cancer.