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

Dhanonjoy C. Saha, Mark E. Astiz, Robert Y. Lin, Eric C. Rackow, Lesley J. Eales

Research output: Contribution to journalArticle

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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 (> 100 μg/ml) stimulated monocytes to release NO that was significantly greater than both the control and LPS-treated monocytes (p <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 <0.01). MPL significantly increased inducible NOS (iNOS) expression as measured by both fluorescent microscopy and flow cytometry (p <0.05). Similarly, both soluble NOS (sNOS) and particulate NOS (pNOS) activity were significantly up-regulated by MPL (p <0.05). Significant correlations were found between pNOS expression and sNOS release (r= 0.72, p <0.0001) and between 12 h NO release and sNOS production (r= 0.44, p <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.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalImmunopharmacology
Volume37
Issue number2-3
DOIs
StatePublished - Oct 1997
Externally publishedYes

Fingerprint

Nitric Oxide Synthase
Monocytes
Nitric Oxide
Up-Regulation
Lipopolysaccharides
Arginase
In Vitro Techniques
monophosphoryl lipid A
Nitric Oxide Synthase Type II
Nitrites
Arginine
Microscopy
Flow Cytometry
Enzymes

Keywords

  • LPS
  • Monocytes
  • MPL
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro. / Saha, Dhanonjoy C.; Astiz, Mark E.; Lin, Robert Y.; Rackow, Eric C.; Eales, Lesley J.

In: Immunopharmacology, Vol. 37, No. 2-3, 10.1997, p. 175-184.

Research output: Contribution to journalArticle

Saha, Dhanonjoy C. ; Astiz, Mark E. ; Lin, Robert Y. ; Rackow, Eric C. ; Eales, Lesley J. / Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro. In: Immunopharmacology. 1997 ; Vol. 37, No. 2-3. pp. 175-184.
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