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Activation of the lipoxygenase pathway in the methionine enkephalin induced respiratory burst in human
1First Department of Medicine, University Medical School, Debrecen, Hungary.
Abstract:
In comparative studies of f-met-Leu-Phe (FMLP) and methionine enkephalin (ME) induced polymorphonuclear leukocyte (PMNL) stimulation the following results were obtained: (i) both FMLP and ME increased the intracellular killing (IK) capability of human PMNLs probably through NADPH oxidase activation, (ii) the ME-induced respiratory burst (RB) differed from the chemotactic peptide FMLP-triggered superoxide generation because the former was not accompanied by the activation of the glutathione system and the duration of the superoxide production was prolonged. The reaction was dependent on lipoxygenation, was potentiated by indomethacin (IM) and was inhibited by nordihidro-guairetic acid (NDGA), (iii) both 14C-arachidonic acid (14C-AA) release and leukotriene B4 (LTB4) synthesis of ME-treated PMNLs were elevated as compared to those of FMLP triggered cells. Our results suggest that lipoxygenation and even an increased LTB4 synthesis are involved in the ME-induced RB of leukocytes.
Insights
Methionine enkephalin (ME) enhances polymorphonuclear leukocyte (PMNL) intracellular killing and triggers a prolonged respiratory burst. This ME-induced response involves lipoxygenation and increased leukotriene B4 synthesis, differing from f-met-Leu-Phe (FMLP) stimulation.
Area of Science:
- Immunology
- Cellular Biology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMNLs) are crucial immune cells involved in pathogen killing.
- Stimulation by chemotactic peptides like f-met-Leu-Phe (FMLP) triggers specific cellular responses.
- Methionine enkephalin (ME), an endogenous opioid peptide, also modulates immune cell function.
Purpose of the Study:
- To comparatively analyze the effects of FMLP and ME on human PMNL activation.
- To elucidate the specific mechanisms underlying ME-induced PMNL responses, particularly the respiratory burst.
- To investigate the role of lipoxygenation and leukotriene synthesis in ME-stimulated PMNLs.
Main Methods:
- Comparative analysis of PMNL stimulation by FMLP and ME.
- Measurement of intracellular killing (IK) capabilities.
- Assessment of respiratory burst (RB) activity, including superoxide generation.
- Quantification of 14C-arachidonic acid (14C-AA) release and leukotriene B4 (LTB4) synthesis.
- Evaluation of the effects of indomethacin (IM) and nordihidro-guairetic acid (NDGA).
Main Results:
- Both FMLP and ME increased PMNL intracellular killing, likely via NADPH oxidase activation.
- ME-induced RB differed from FMLP-induced superoxide generation; it was prolonged and not associated with glutathione system activation.
- ME stimulation led to increased 14C-arachidonic acid release and LTB4 synthesis compared to FMLP.
- The ME-induced RB was dependent on lipoxygenation, potentiated by IM, and inhibited by NDGA.
Conclusions:
- Methionine enkephalin (ME) enhances PMNL intracellular killing and induces a distinct respiratory burst.
- Lipoxygenation and elevated leukotriene B4 synthesis are key components of the ME-induced PMNL respiratory burst.
- These findings highlight differential signaling pathways activated by ME and FMLP in PMNLs.