Am. J. Respir. Cell Mol. Biol., Vol 16, No. 4, Apr 1997, 413-420.
Species differences in NO formation by rat and hamster alveolar macrophages in vitro
M Dorger, NK Jesch, G Rieder, MR Hirvonen, K Savolainen, F Krombach and K Messmer
Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Germany.
Nitric oxide (NO) is a cellular mediator and regulator of multiple biologic
functions. NO released by alveolar macrophages (AM) is suggested to play a
role in mediating pulmonary injury. In murine and rat macrophages, the
expression of inducible NO synthase (iNOS) and the release of NO are well
established. However, the existence of such a pathway in other species
remains controversial. In this study, we examined NO production and iNOS
expression by AM from rats and hamsters, two laboratory animal species that
are characterized by their disparate pulmonary responses to various inhaled
irritants/toxicants. AM were treated with lipopolysaccharide (LPS),
interferon-gamma (IFN- gamma), or tumor necrosis factor-alpha (TNF-alpha)
in vitro, and nitrite, the stable oxidation product of NO, was assayed by
the Griess reaction. Rat AM produced NO in a dose- and time-dependent
manner upon stimulation with LPS and/or IFN-gamma, but not with TNF-alpha.
Surprisingly, hamster AM did not release detectable levels of NO after the
same treatment. Although iNOS expression was demonstrated in rat AM by
immunocytochemical and Western blot analyses, no induction of iNOS
expression could be found in hamster AM. Using reverse transcriptase-
polymerase chain reaction (RT-PCR) analysis, we found that rat and hamster
AM could be induced to express iNOS mRNA after treatment with LPS and
IFN-gamma. The results presented here indicate that hamster AM, in contrast
to rat AM, lack the ability to express iNOS protein and to generate NO in
response to LPS, IFN-gamma, or TNF-alpha in vitro. In conclusion, our data
suggest striking differences in iNOS regulation and NO production by AM
from rats and hamsters, two rodent species that are commonly used in
biomedical research and well-known for their disparate responses to
pulmonary irritants/toxicants.
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Copyright © 1997 American Thoracic Society.
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