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Bidirectional effect of met-enkephalin on macrophage effector functions
Molecular and Cellular Biochemistry
|February 1, 1986
Summary
Met-enkephalin (ME) has dual effects on rat macrophages. Low concentrations stimulate cytotoxicity and inhibit phagocytosis via opioid receptors, while high concentrations do the opposite, involving calcium influx and cAMP.
Area of Science:
- Immunology
- Neuroendocrinology
- Cellular Physiology
Background:
- Met-enkephalin (ME), an endogenous opioid peptide, modulates immune cell function.
- Macrophages play critical roles in innate and adaptive immunity, including phagocytosis and cytotoxicity.
- The precise mechanisms by which ME influences macrophage functional activities remain incompletely understood.
Purpose of the Study:
- To investigate the bimodal effects of Met-enkephalin (ME) on rat peritoneal macrophage (PM) functions.
- To elucidate the underlying cellular and molecular mechanisms mediating these concentration-dependent effects.
- To explore the roles of ion fluxes, second messengers (cGMP, cAMP), and specific receptors in ME's action.
Main Methods:
- Measurement of antibody-dependent cellular cytotoxicity (ADCC) and Fc gamma receptor (Fc gamma R)-mediated phagocytosis.
- Assessment of intracellular Na+ and Ca2+ fluxes using ion-sensitive indicators.
- Quantification of intracellular cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) levels.
- Pharmacological manipulation using naloxone, verapamil, and enkephalinase inhibitors.
Main Results:
- Low ME concentrations (10(-9)-10(-7)M) enhanced ADCC and decreased Fc gamma R phagocytosis, associated with Na+ influx and Ca2+ efflux, and increased cGMP.
- High ME concentrations (10(-6)-10(-5)M) decreased ADCC and enhanced Fc gamma R phagocytosis, linked to Na+ and Ca2+ influx, and increased cAMP.
- ME's effects were partially mediated by delta opioid receptors at low concentrations, while high concentrations involved Ca2+ influx, adenylate cyclase activation, and PM-enkephalinase inhibition.
Conclusions:
- Met-enkephalin exhibits concentration-dependent, bimodal effects on rat macrophage functions.
- Low ME concentrations act via delta opioid receptors, influencing cGMP levels.
- High ME concentrations involve calcium influx, cAMP activation, and inhibition of PM-enkephalinase, independent of specific opioid receptors.