Both, pge2 and nitric oxide, sequentially mediate the tnf[alpha]
-induced inhibition of phosphatidylcholine synthesis by human type ii
pneumocytes.
Vara, E., J. Arias-D[acute]iaz, C. Garc[acute]ia, J. Hern[acute]andez,
J. L. Balibrea.
Departments of Biochemistry (Facultad de Medicina) and Surgery
(Hospital San Carlos), Universidad Complutense, 28040 Madrid,
Spain.
APStracts 3:0053L, 1996.
TNF[alpha]-induced inhibition of surfactant synthesis participates in
the pathogenesis of the adult respiratory distress syndrome. We
examined the ability of human type II pneumocytes to produce nitric
oxide (NO) in the presence of TNF[alpha], and the role of NO and PGE2
in the transduction of the cytokine signal. Multiple organ donors
were used as a source of lung tissue. After 24 h-preculture, type II
pneumocytes were cultured for 18 h in the presence or absence of
additives. The D-(U-14C)glucose incorporation into
phosphatidylcholine (PC) was selectively inhibited by TNF[alpha],
PGE2, sodium nitroprusside (NTP), or 8-Br-cGMP. The effect of
TNF[alpha] was attenuated by indomethacin, N -nitro-L-arginine methyl
ester (NAME), or methylene blue (MB). The effect of PGE2 was
attenuated by NAME, while that of NTP was reverted by MB, but not by
indomethacin. TNF[alpha] induced an increase in PGE2 (4.31+/-0.27 vs
1.65+/-0.17 pg/[mu]g protein, n=10, p<.01) and cGMP cell content
and in the NO release to the medium (3.10+/-0.14 vs 1.19+/-0.11
nmol/[mu]g protein, n=10, p<.01). NAME did not affect PGE2
production, while indomethacin blunted NO generation. Our results
suggest that NO generation, secondary to PGE2 production, is
responsible for the TNF[alpha]-induced inhibition of PC synthesis by
human type II pneumocytes.
Received 6 June 1995; accepted in final form 14 March 1996.
APS Manuscript Number L182-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96