Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages. 1997

M J Thomassen, and L T Buhrow, and M J Connors, and F T Kaneko, and S C Erzurum, and M S Kavuru
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195-5038, USA. thomasm@cesmtp.ccf.org

High levels of nitric oxide (NO) have been reported in exhaled air of asthmatic individuals. Because alveolar macrophages (AM) are major producers of cytokines, and bronchoalveolar lavage fluid (BALF) from asthmatic individuals contains increased levels of inflammatory cytokines, this study was undertaken to determine whether NO modified the production of inflammatory cytokines by human AM. AM were obtained from normal volunteers by fiberoptic bronchoscopy. Tumor necrosis factor-alpha (TNF-alpha) production stimulated by lipopolysaccharide (LPS; 0.5 microg/ml) was measured with an enzyme-linked immunosorbent assay (ELISA). NO generated from 2,2-(hydroxynitrosohydrazono)-bis-ethanamine (DETA NONOate) (0.1 to 1.0 mM) inhibited TNF-alpha secretion in a dose-dependent manner. At 1 mM DETA NONOate, mean inhibition (+/- SEM) of TNF-alpha secretion was 56 +/- 4% (P = 0.002). To determine whether this effect was cytokine specific, interleukin-1beta (IL-1beta) and macrophage inflammatory protein-1alpha (MIP-1alpha) were evaluated, and DETA NONOate was also found to inhibit both of these cytokines. Basal cytokine levels from unstimulated AM were unaffected by NO. These findings indicate that NO is a potent inhibitor of cytokine production by stimulated human AM.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009603 Nitroso Compounds Organic compounds containing the nitroso (-N Compounds, Nitroso
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016676 Macrophages, Alveolar Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Alveolar Macrophages,Macrophages, Pulmonary,Pulmonary Macrophages,Macrophage, Pulmonary,Pulmonary Macrophage,Alveolar Macrophage,Macrophage, Alveolar
D054405 Chemokine CCL3 A CC chemokine with specificity for CCR1 RECEPTORS and CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES; and a variety of other immune cells. This chemokine is encoded by multiple genes. CCL3 Chemokine,CCL3L1 Chemokine,CCL3L2 Chemokine,CCL3L3 Chemokine,Chemokine CCL3L1,Chemokine CCL3L2,Chemokine CCL3L3,BB-10010,Chemokine (C-C Motif) Ligand 3,Chemokine (C-C Motif) Ligand 3-Like 1,Chemokine (C-C Motif) Ligand 3-Like 2,LD78alpha Chemokine,LD78beta Chemokine,MIP-1alpha,Macrophage Inflammatory Protein 1-alpha,Small Inducible Cytokine A3,BB 10010,BB10010,CCL3, Chemokine,CCL3L1, Chemokine,CCL3L2, Chemokine,CCL3L3, Chemokine,Chemokine, CCL3,Chemokine, CCL3L1,Chemokine, CCL3L2,Chemokine, CCL3L3,Chemokine, LD78alpha,Chemokine, LD78beta,Macrophage Inflammatory Protein 1 alpha
D054407 Chemokine CCL4 A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes. CCL4 Chemokine,CCL4L1 Chemokine,CCL4L2 Chemokine,Chemokine CCL4L1,Chemokine CCL4L2,MIP-1beta,Macrophage Inflammatory Protein 1-beta,Macrophage Inflammatory Protein-1beta2,CCL4, Chemokine,CCL4L1, Chemokine,CCL4L2, Chemokine,Chemokine, CCL4,Chemokine, CCL4L1,Chemokine, CCL4L2,Inflammatory Protein-1beta2, Macrophage,MIP 1beta,Macrophage Inflammatory Protein 1 beta,Macrophage Inflammatory Protein 1beta2
D019402 Macrophage Inflammatory Proteins Heparin-binding proteins that exhibit a number of inflammatory and immunoregulatory activities. Originally identified as secretory products of MACROPHAGES, these chemokines are produced by a variety of cell types including NEUTROPHILS; FIBROBLASTS; and EPITHELIAL CELLS. They likely play a significant role in respiratory tract defenses. Macrophage Inflammatory Protein,Macrophage Inflammatory Protein-1,Inflammatory Protein, Macrophage,Inflammatory Protein-1, Macrophage,Inflammatory Proteins, Macrophage,Macrophage Inflammatory Protein 1,Protein, Macrophage Inflammatory,Protein-1, Macrophage Inflammatory

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