M. Abe et al., LUNG-CANCER CELL-LINES INHIBIT LEUKOTRIENE B-4 PRODUCTION BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES AT THE LEVEL OF PHOSPHOLIPASE A(2), American journal of respiratory cell and molecular biology, 15(5), 1996, pp. 565-573
We studied cellular interactions between human polymorphonuclear leuko
cytes (PMN) and lung cancer cell lines by investigating the influence
of cancer cells on the production of leukotriene B-4 (LTB(4)) and supe
roxide anion (O-2(-)) by stimulated PMN. Of the nine cancer cell lines
established from human lung cancers that we examined, H23 cells showe
d the highest LTA(4) hydrolase activity. When PMN were stimulated by t
he calcium ionophore A23187 in the presence of H23 cells, the producti
on of LTB(4), 5(S)-hydroxyeicosatetraenoic acid (5-HETE), and 12(S)-hy
droxyeicosatetraenoic acid (12-HETE) decreased in a dose-dependent man
ner. On the contrary, H23 did not inhibit O-2(-) production by PMN. Tw
o other cell lines (N417 and Q9) caused similar inhibition of LTB(4) p
roduction 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-dep
endently 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 in
hibited C-14 release from [C-14]AA prelabeled PMN in a cell number-dep
endent manner in the buffer, with and without albumin. The supernatant
of H23 cells also inhibited the production of LTB(4) by PMN stimulate
d by A23187, as did the addition of H23 lysate or its 10(4) X g centri
fugation supernatant. While neither the 10(5) x g supernatant (cytosol
) nor the pellet (microsome) exhibited inhibitory activity, the combin
ation of the separated cytosol and microsomal fractions restored the i
nhibitory activity. Furthermore, addition of the 10(4) x g supernatant
of Q9 lysate to partially purified human cytosolic PLA(2) inhibited P
LA(2) activity in a dose-dependent manner. Our results indicate that t
he 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.