Concentration-dependent effect of met-enkephalin on human polymorphonuclear leukocytes

Area of Science:

• Immunology
• Neuroendocrinology
• Cellular Signaling

Background:

• Met-enkephalin is an endogenous opioid peptide with known immunomodulatory roles.
• Opioid receptors are expressed on immune cells, including polymorphonuclear leukocytes (PMNLs).
• The precise mechanisms by which met-enkephalin influences immune cell function, particularly ADCC, require further elucidation.

Purpose of the Study:

• To investigate the dose-dependent effects of met-enkephalin on antibody-dependent cell-mediated cytotoxicity (ADCC) in human PMNLs.
• To explore the intracellular signaling pathways involved in met-enkephalin's modulation of ADCC.
• To determine the role of opiate receptors and enkephalinase in these effects.

Main Methods:

• Human PMNLs were treated with varying concentrations of met-enkephalin (10(-9)M to 10(-5)M).
• ADCC activity was measured.
• Intracellular levels of calcium (Ca2+), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) were assessed.
• Effects of naloxone (opiate receptor antagonist) and puromycin (enkephalinase inhibitor) were evaluated.

Main Results:

• Low concentrations (10(-9)-10(-7)M) of met-enkephalin stimulated ADCC via naloxone-sensitive opiate receptors, increasing cytoplasmic Ca2+ and cGMP.
• Higher concentrations (10(-6)-10(-5)M) elevated cAMP and induced a rapid 45Ca2+ influx, suppressing ADCC.
• The suppressive effect at higher concentrations was abolished by puromycin, suggesting involvement of enkephalinase.
• A link between met-enkephalin's suppressive effect, enkephalinase, and protein kinase C was indicated.

Conclusions:

• Met-enkephalin exhibits dose-dependent modulation of human PMNL ADCC.
• Low-dose met-enkephalin enhances ADCC through opiate receptors, impacting Ca2+ and cGMP.
• High-dose met-enkephalin inhibits ADCC via a mechanism involving enkephalinase, cAMP, and potentially protein kinase C.