Lung cancer cell lines inhibit leukotriene B-4 production by human polymorphonuclear leukocytes at the level of phospholipase A(2)

We studied cellular interactions between human polymorphonuclear leukocytes (PMN) and lung cancer cell lines by investigating the influence of cancer cells on the production of leukotriene B-4 (LTB(4)) and superoxide anion (O-2(-)) by stimulated PMN. Of the nine cancer cell lines established from human lung cancers that we examined, H23 cells showed the highest LTA(4) hydrolase activity. When PMN were stimulated by the calcium ionophore A23187 in the presence of H23 cells, the production of LTB(4), 5(S)-hydroxyeicosatetraenoic acid (5-HETE), and 12(S)-hydroxyeicosatetraenoic acid (12-HETE) decreased in a dose-dependent manner. On the contrary, H23 did not inhibit O-2(-) production by PMN. Two other cell lines (N417 and Q9) caused similar inhibition of LTB(4) production by PMN. These three cancer cell lines alone did not generate any metabolites of the arachidonic acid (AA) lipoxygenase pathway or any Oz upon stimulation with A23187 alone. The addition of AA dose-dependently reversed the H23-induced inhibition of LTB(4), 5-HETE, and 12-HETE production by PMN, suggesting inhibition at the phospholipase A(2) (PLA(2)) level. Furthermore, addition of the cancer cell line Q9 inhibited C-14 release from [C-14]AA prelabeled PMN in a cell number-dependent manner in the buffer, with and without albumin. The supernatant of H23 cells also inhibited the production of LTB(4) by PMN stimulated by A23187, as did the addition of H23 lysate or its 10(4) X g centrifugation supernatant. While neither the 10(5) x g supernatant (cytosol) nor the pellet (microsome) exhibited inhibitory activity, the combination of the separated cytosol and microsomal fractions restored the inhibitory activity. Furthermore, addition of the 10(4) x g supernatant of Q9 lysate to partially purified human cytosolic PLA(2) inhibited PLA(2) activity in a dose-dependent manner. Our results indicate that the lung cancer cell lines used in our study inhibit LTB(4) production by human PMN through inhibition of phospholipase A(2) activity, which may contribute to a predisposition to pulmonary infections in patients with lung cancer.