JH Persoons, K Schornagel, FF Tilders, J De Vente, F Berkenbosch and G Kraal
Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, The Netherlands.

The effect of nitric oxide on the lipopolysaccharide (LPS)-induced cytokine production by alveolar macrophages was studied. When alveolar macrophages were cultured, substantial amounts of interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha(TNF-alpha), and nitric oxide are produced upon stimulation with LPS. Inhibition of the nitric oxide production by the L-arginine analogue N(G)-monomethyl-L- arginine (NMMA), resulted in an increase of IL-1(beta) and IL-6, whereas the TNF-alpha concentrations remained unchanged, suggesting specific inhibitory effects of nitric oxide on the LPS-stimulated cytokine production by alveolar macrophages. The observed cytokine- modulation properties of nitric oxide did not result from cytotoxic actions of the oxidation of L-arginine on macrophages, since nitric oxide synthesis did not affect the viability of the alveolar macrophages. Conversely the nitric oxide donor S-nitroso-N-acetyl-D, L- penicillamine (SNAP) induced dose-dependent inhibition of IL-1 production in LPS-stimulated alveolar macrophages in which endogenous nitric oxide production was blocked. The results indicate that nitric oxide can affect the LPS-induced IL-1beta and IL-6 secretion by alveolar macrophages in an autoregulatory way and are discussed in view of the important physiologic consequences this autoregulation by nitric acid oxide may have.

This article has been cited by other articles:

				M. Miyamoto, M. Tomaki, J. Lotvall, and A. Linden {beta}-Adrenoceptor stimulation and neutrophil accumulation in mouse airways Eur. Respir. J., August 1, 2004; 24(2): 231 - 237. [Abstract] [Full Text] [PDF]

				S. Fiorucci, E. Distrutti, A. Mencarelli, G. Rizzo, A. R. D. Lorenzo, M. Baldoni, P. del Soldato, A. Morelli, and J. L. Wallace Cooperation between Aspirin-Triggered Lipoxin and Nitric Oxide (NO) Mediates Antiadhesive Properties of 2-(Acetyloxy)benzoic Acid 3-(Nitrooxymethyl)phenyl Ester (NCX-4016) (NO-Aspirin) on Neutrophil-Endothelial Cell Adherence J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1174 - 1182. [Abstract] [Full Text] [PDF]

				H. Miyakawa, K. Sato, T. Shinbori, T. Okamoto, Y. Gushima, M. Fujiki, and M. Suga Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice Eur. Respir. J., March 1, 2002; 19(3): 447 - 457. [Abstract] [Full Text] [PDF]

				S. Yang, V. A. Porter, D. N. Cornfield, C. Milla, A. Panoskaltsis-Mortari, B. R. Blazar, and I. Y. Haddad Effects of oxidant stress on inflammation and survival of iNOS knockout mice after marrow transplantation Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L922 - L930. [Abstract] [Full Text] [PDF]

				D. Blond, H. Raoul, R. Le Grand, and D. Dormont Nitric Oxide Synthesis Enhances Human Immunodeficiency Virus Replication in Primary Human Macrophages J. Virol., October 1, 2000; 74(19): 8904 - 8912. [Abstract] [Full Text]

				H.-P. KUO, C.-H. WANG, K.-S. HUANG, H.-C. LIN, C.-T. YU, C.-Y. LIU, and L.-C. LU Nitric Oxide Modulates Interleukin-1beta and Tumor Necrosis Factor-alpha Synthesis by Alveolar Macrophages in Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 192 - 199. [Abstract] [Full Text]

				R. A. Schroeder, C. Cai, and P. C. Kuo Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages Am J Physiol Cell Physiol, September 1, 1999; 277(3): C523 - C530. [Abstract] [Full Text] [PDF]

				J. A. Dye, K. B. Adler, J. H. Richards, and K. L. Dreher Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L498 - L510. [Abstract] [Full Text] [PDF]

				W. S. Cruz, J. A. Corbett, W. J. Longmore, and M. A. Moxley Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L263 - L268. [Abstract] [Full Text] [PDF]

				D. R. Meldrum, B. D. Shames, X. Meng, D. A. Fullerton, R. C. McIntyre Jr, F. L. Grover, and A. H. Harken Nitric oxide downregulates lung macrophage inflammatory cytokine production Ann. Thorac. Surg., August 1, 1998; 66(2): 313 - 317. [Abstract] [Full Text] [PDF]

				R. M. Schapira, J. H. Wiessner, J. F. Morrisey, U. A. Almagro, and L. D. Nelin L-Arginine Uptake and Metabolism by Lung Macrophages and Neutrophils Following Intratracheal Instillation of Silica In Vivo Am. J. Respir. Cell Mol. Biol., August 1, 1998; 19(2): 308 - 315. [Abstract] [Full Text]

				N. Hirji, T.-J. Lin, E. Bissonnette, M. Belosevic, and A. D. Befus Mechanisms of Macrophage Stimulation Through CD8: Macrophage CD8{alpha} and CD8{beta} Induce Nitric Oxide Production and Associated Killing of the Parasite Leishmania major J. Immunol., June 15, 1998; 160(12): 6004 - 6011. [Abstract] [Full Text] [PDF]

				M. J. Thomassen, L. T. Buhrow, M. J. Connors, F. Kaneko, S. C. Erzurum, and M. S. Kavuru Nitric Oxide Inhibits Inflammatory Cytokine Production by Human Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 279 - 283. [Abstract] [Full Text]

				J. H. A. Persoons, N. M. Moes, E. Broug-Holub, K. Schornagel, F. J. H. Tilders, and G. Kraal Acute and Long-term Effects of Stressors on Pulmonary Immune Functions Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 203 - 208. [Abstract] [Full Text]

				L. Yan, S. Wang, S. P. Rafferty, R. A. Wesley, and R. L. Danner Endogenously Produced Nitric Oxide Increases Tumor Necrosis Factor-alpha Production in Transfected Human U937 Cells Blood, August 1, 1997; 90(3): 1160 - 1167. [Abstract] [Full Text] [PDF]