Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Inhaled nitric oxide primes lung macrophages to produce reactive oxygen and nitrogen intermediates.

Authors: Weinberger, B; Fakhrzadeh, L; Heck, D E; Laskin, J D; Gardner, C R; Laskin, D L

Published In Am J Respir Crit Care Med, (1998 Sep)

Abstract: Inhaled nitric oxide is a selective pulmonary vasodilator used for the treatment of pulmonary hypertension. The potential adverse effects of inhaled nitric oxide are unknown and represent the focus of the present studies. Whereas inhalation of nitric oxide (10 to 100 ppm, 5 h) by Balb/c mice had no effect on the number or type of cells recovered from the lung, a dose-related increase in bronchoalveolar lavage protein was observed, suggesting that nitric oxide induces alveolar epithelial injury. To determine if this was associated with altered alveolar macrophage activity, we quantified production of reactive oxygen and nitrogen intermediates by these cells. Interferon-gamma, alone or in combination with lipopolysaccharide (LPS), induced expression of inducible nitric oxide synthase (iNOS) protein and nitric oxide production by alveolar macrophages. Cells from mice exposed to 20 to 100 ppm nitric oxide produced significantly more nitric oxide and expressed greater quantities of iNOS than cells from control animals. Superoxide anion production and peroxynitrite generation by alveolar macrophages were also increased after exposure of mice to nitric oxide. This was correlated with increased antinitrotyrosine antibody binding to macrophages in histologic sections. Taken together, these data demonstrate that inhaled nitric oxide primes lung macrophages to release reactive oxygen and nitrogen intermediates. Increased production of these mediators by macrophages following inhalation of nitric oxide may contribute to tissue injury.

PubMed ID: 9731028 Exiting the NIEHS site

MeSH Terms: Administration, Inhalation; Animals; Antibodies/diagnostic use; Bronchoalveolar Lavage Fluid/chemistry; Dose-Response Relationship, Drug; Epithelial Cells/drug effects; Interferon Type II/administration & dosage; Interferon Type II/pharmacology; Lipopolysaccharides/pharmacology; Lung/cytology; Lung/drug effects*; Lung/enzymology; Macrophages, Alveolar/drug effects*; Macrophages, Alveolar/enzymology; Macrophages, Alveolar/metabolism; Male; Mice; Mice, Inbred BALB C; Nitrates/metabolism; Nitric Oxide Synthase Type II; Nitric Oxide Synthase/biosynthesis; Nitric Oxide Synthase/metabolism; Nitric Oxide/administration & dosage; Nitric Oxide/pharmacology*; Nitrogen/metabolism*; Oxidants/metabolism; Proteins/analysis; Pulmonary Alveoli/cytology; Pulmonary Alveoli/drug effects; Reactive Oxygen Species/metabolism*; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Superoxides/metabolism; Tyrosine/analogs & derivatives; Tyrosine/metabolism; Vasodilator Agents/administration & dosage; Vasodilator Agents/pharmacology*

Back
to Top