Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages

Ming Hai Wang, George W. Cox, Teizo Yoshimura, Lynn A. Sheffler, Alison Skeel, Edward J. Leonard

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Abstract

Human serum macrophage-stimulating protein (MSP) is a disulfide-linked heterodimer that induces motile and phagocytic activity of mouse resident peritoneal macrophages. In this work, we found that MSP blocked the increase in macrophage nitric oxide synthase mRNA, as well as the associated increase in nitric oxide production, that occurred in response to several stimuli. These included bacterial products and mammalian cytokines: endotoxin, and interferon-γ plus endotoxin, interleukin-2, or tumor necrosis factor-α. The inhibition by MSP of induction of nitric oxide synthase mRNA and nitric oxide secretion was concentration-dependent. The concentration of MSP that caused maximal inhibition of nitric oxide production was comparable with the optimum for stimulation of macrophage motile and phagocytic activity. Time course studies showed that nitrite was first detected in culture fluid about 8 h after endotoxin stimulation, and it accumulated at a linear rate during the ensuing 16 h. Inhibition by MSP occurred during the 8-h lipopolysaccharide (LPS) induction period; inhibition was maximal when MSP and LPS were added together and decreased progressively to no inhibition as the interval between LPS and MSP addition increased to 11 h.

Original languageEnglish
Pages (from-to)14027-14031
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number19
Publication statusPublished - May 13 1994
Externally publishedYes

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Macrophages
Endotoxins
Nitric Oxide
Cytokines
Lipopolysaccharides
Nitric Oxide Synthase
Messenger RNA
Time and motion study
Peritoneal Macrophages
Nitrites
macrophage stimulating protein
Disulfides
Interferons
Interleukin-2
Tumor Necrosis Factor-alpha
Fluids
Serum

ASJC Scopus subject areas

  • Biochemistry

Cite this

Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages. / Wang, Ming Hai; Cox, George W.; Yoshimura, Teizo; Sheffler, Lynn A.; Skeel, Alison; Leonard, Edward J.

In: Journal of Biological Chemistry, Vol. 269, No. 19, 13.05.1994, p. 14027-14031.

Research output: Contribution to journalArticle

Wang, Ming Hai ; Cox, George W. ; Yoshimura, Teizo ; Sheffler, Lynn A. ; Skeel, Alison ; Leonard, Edward J. / Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 19. pp. 14027-14031.
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