title: Lung cancer cell lines inhibit leukotriene B4 production by human polymorphonuclear leukocytes at the level of phospholipase A2.
abstract: 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 B4 (LTB4) and superoxide anion (O2-) by stimulated PMN. Of the nine cancer cell lines established from human lung cancers that we examined, H23 cells showed the highest LTA4 hydrolase activity. When PMN were stimulated by the calcium ionophore A23187 in the presence of H23 cells, the production of LTB4, 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 O2- production by PMN. Two other cell lines (N417 and Q9) caused similar inhibition of LTB4 production by PMN. These three cancer cell lines alone did not generate any metabolites of the arachidonic acid (AA) lipoxygenase pathway or any O2- upon stimulation with A23187 alone. The addition of AA dose-dependently reversed the H23-induced inhibition of LTB4, 5-HETE, and 12-HETE production by PMN, suggesting inhibition at the phospholipase A2 (PLA2) level. Furthermore, addition of the cancer cell line Q9 inhibited 14C release from [14C]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 LTB4 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 PLA2 inhibited PLA2 activity in a dose-dependent manner. Our results indicate that the lung cancer cell lines used in our study inhibit LTB4 production by human PMN through inhibition of phospholipase A2 activity, which may contribute to a predisposition to pulmonary infections in patients with lung cancer.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Matsuki
authors.forename: M
authors.initials: M
authors.lastname: Domae
authors.forename: H
authors.initials: H
authors.lastname: Kuwata
authors.forename: I
authors.initials: I
authors.lastname: Kudo
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: N
authors.initials: N
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Mitsuyama
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000378:metabolism; D008175:Lung Neoplasms; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013347:Subcellular Fractions; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; D013481:Superoxides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D007213:Indomethacin