Inhibition of alveolar type ii cell atp and surfactant synthesis by
nitric oxide.
Haddad, Imad Y., Sha Zhu, John Crow, Elaine Barefield, Thomas Gadilhe,
and Sadis Matalon.
Departments of Pediatrics, Anesthesiology, Physiology and
Biophysics, University of Alabama at Birmingham, Birmingham, AL
35233-6810
APStracts 3:0006L, 1996.
Alveolar type II (ATII) cells, are often exposed to increased
concentration of endogenous and exogenous nitric oxide (.NO).
Exposure of freshly isolated rat ATII cells for 2 h to 1-3 [mu]M .NO,
generated by S-nitroso-N-penicillamine (SNAP), spermine NONOate or 3
-morpholino-sydnonimine (SIN-1) in the presence of superoxide
dismutase, resulted in approximately 60% decrease in the rate of
surfactant synthesis, as measured by the rate of incorporation of
[methyl-3H]-choline into phosphatidylcholine, and 60-80% inhibition
of cellular adenosine 5'-triphosphate (ATP) levels, as determined by
bioluminescence. Similar results were obtained after incubation of
ATII cells to authentic peroxynitrite (0.5 mM), but not SIN-1, a
putative generator of peroxynitrite. Addition of oxyhemoglobin (HbO2;
20 [mu]M) into the medium, which scavenged .NO, or enhancement of
ATII glutathione levels by pre-incubation with glutathione ester (5
mM), totally prevented the NONOate (100 [mu]M) inhibition of cellular
ATP. In contrast to the in vitro findings, normal levels of ATP and
lipid synthesis were measured in ATII cells, isolated from the lungs
of rats that breathed .NO gas (80 ppm) in 21% O2 for 2 h (n=4). This
lack of effect may be due either to the presence of various
antioxidants (such as glutathione) in the epithelial lining fluid, or
the relatively low concentrations of .NO reaching the alveolar
epithelium. We conclude that .NO and peroxynitrite, at concentrations
likely to be encountered in vivo during inflammation, decreases ATII
cell energy stores and surfactant synthesis, which may lead to
derangement of important physiological functions.
Received 23 August 1995; accepted in final form 27 December 1995.
APS Manuscript Number L256-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96