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Effect of muramyl peptides and tumor necrosis factor on oxidative responses of human blood phagocytes
1Laboratory of Immunopharmacology, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Abstract:
Adjuvant muramyl dipeptides enhanced the intracellular oxidative burst induced by phorbol myristate acetate in purified human polymorphonuclear (PMN) cells and in monocytes. A stronger priming effect was obtained when muramyl dipeptide was conjugated to a protein carrier. Recombinant human tumor necrosis factor (TNF) did not modify the level of intracellular NBT reduction in PMA-stimulated PMN, although it slightly increased the secretion of superoxide anion. In contrast, TNF enhanced the intracellular oxidative burst of monocytes even at the concentration of 10 pg/ml. In human PMN only, the combination of TNF and muramyl dipeptide induced a higher oxidative response than each stimulant alone.
Insights
Adjuvant muramyl dipeptides and tumor necrosis factor (TNF) boost immune cell oxidative bursts. Conjugating muramyl dipeptide to carriers enhances this effect, particularly in monocytes and human polymorphonuclear (PMN) cells.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Adjuvant muramyl dipeptides (MDPs) are known immunomodulators.
- Tumor necrosis factor (TNF) plays a critical role in immune responses.
Purpose of the Study:
- To investigate the synergistic effects of MDPs and TNF on the oxidative burst in human immune cells.
- To compare the efficacy of unconjugated MDPs versus protein-conjugated MDPs.
Main Methods:
- Purified human polymorphonuclear (PMN) cells and monocytes were isolated.
- Cells were stimulated with phorbol myristate acetate (PMA) in the presence or absence of MDPs and/or TNF.
- Intracellular oxidative burst was measured via NBT reduction and superoxide anion secretion.
Main Results:
- MDPs enhanced PMA-induced oxidative burst in both PMNs and monocytes.
- Protein-conjugated MDPs showed a stronger priming effect than unconjugated MDPs.
- TNF enhanced monocyte oxidative burst but had minimal effect on PMA-stimulated PMNs, except for a slight increase in superoxide secretion.
- Combined TNF and MDP treatment resulted in a significantly higher oxidative response in human PMNs compared to individual treatments.
Conclusions:
- MDPs, especially when conjugated to proteins, are potent enhancers of cellular oxidative burst.
- TNF exhibits differential effects on PMNs and monocytes regarding oxidative burst.
- Combination therapy of TNF and MDPs shows promise for potentiating immune cell responses in human PMNs.