Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro

Saha, D. C., Astiz, M. E., Lin, R. Y., Rackow, E. C. and Eales-Reynolds, Lesley-Jane ORCID: 0000-0002-9906-2484 (1997) Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro. Immunopharmacology, 37 (2-3). pp. 175-184. ISSN 0162-3109

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Abstract

Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) with reduced toxicity which has been shown to modulate various immune functions in monocytes. We examined whether human monocytes can be stimulated to produce nitric oxide (NO) and its catalytic enzyme nitric oxide synthase (NOS). Monocytes were stimulated with LPS or MPL and both NOS and NO (as nitrite) production were measured. MPL at high doses (\textgreater 100 micrograms/ml) stimulated monocytes to release NO that was significantly greater than both the control and LPS-treated monocytes (p \textless 0.05). NO release by control cells and the LPS treated cells was not significantly different. Both arginase and N-monomethyl arginine (NMLA) inhibited the MPL stimulated release of NO (p \textless 0.01). MPL significantly increased inducible NOS (iNOS) expression as measured by both fluorescent microscopy and flow cytometry (p \textless 0.05). Similarly, both soluble NOS (sNOS) and particulate NOS (pNOS) activity were significantly up-regulated by MPL (p \textless 0.05). Significant correlations were found between pNOS expression and sNOS release (r = 0.72, p \textless 0.0001) and between 12 h NO release and sNOS production (r = 0.44, p \textless 0.005). These experiments confirm that human monocytes can be stimulated with MPL to produce NO in vitro and suggest that up-regulation of pNOS does not preclude NO release.

Item Type: Article
Uncontrolled Keywords: Humans, Leukocytes, Mononuclear, Adjuvants, Immunologic, Lipid A, Lipopolysaccharides, Up-Regulation, Arginase, Enzyme Inhibitors, Isoenzymes, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, omega-N-Methylarginine, Stimulation, Chemical
Subjects: Medicine and health
Depositing User: Lesley-Jane Eales-Reynolds
Date Deposited: 20 May 2018 08:26
Last Modified: 21 May 2018 11:49
URI: http://repository.uwl.ac.uk/id/eprint/5062

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