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Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages.

Authors
Miles-PR; Bowman-L; Rao-KMK; Baatz-JE; Huffman-L
Source
Am J Physiol, Lung Cell Mol Physiol 1999 Jan; 276(1):186-196
NIOSHTIC No.
20027773
Abstract
The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide ( NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. NO produced by the cells in response to LPS is due to an inducible NO synthase (iNOS). Surfactant inhibits LPS-induced NO formation in a concentration-dependent manner; NO production is inhibited by about 50 and about 75% at surfactant levels of 100 and 200 microg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an about 80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits NO formation in a concentration-dependent manner; NO production is inhibited by about 50 and about 90% at SP-B levels of 1-2 and 10 microg/ml, respectively. These results show that lung surfactant inhibits LPS-induced NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.
Keywords
Lung-cells; Alveolar-cells; Physiological-chemistry; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders; Blood-disorders; Lung-fibrosis; Nitrogen-compounds; Nitrogen-oxides; Nitrous-oxides; Statistical-analysis; Surfactants
CODEN
APLPE7
CAS No.
10102-43-9
Publication Date
19990101
Document Type
Journal Article
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1040-0605
NIOSH Division
HELD
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
WV; SC
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