Modulation of human neutrophil function by endogenous opiate enkephalins

Area of Science:

• Neuroimmunology
• Endocrinology
• Cellular Immunology

Background:

• Natural opiates, enkephalins (EKs), were previously thought to be exclusive to the central nervous system.
• Recent evidence indicates EKs are released from adrenal glands upon sympathetic activation or trauma.
• The peripheral functions of EKs, particularly on immune cells, remain largely unexplored.

Purpose of the Study:

• To investigate the influence of synthetic enkephalins on human polymorphonuclear leukocytes (neutrophils).
• To determine if enkephalins affect peripheral immune cell functions, such as degranulation, chemotaxis, and morphology.

Main Methods:

• Evaluation of synthetic leucine enkephalin (leuEK) and methionine enkephalin (metEK) on neutrophil functions.
• Use of protease-resistant methionine enkephalin-amide (metEKamide) for enhanced stability.
• Assays included beta-glucuronidase and lysozyme release for degranulation, under-agarose chemotaxis, and scanning electron microscopy for morphology.

Main Results:

• MetEKamide induced neutrophil degranulation at concentrations of 10(-3) and 10(-4) mmol/L.
• MetEKamide enhanced neutrophil responsiveness to low concentrations of formyl-methionyl-leucyl-phenyl-alanine (FMLP), indicating increased chemokinesis.
• MetEKamide altered neutrophil morphology and exhibited chemotactic activity at 10(-2) mmol/L.

Conclusions:

• Enkephalins, specifically metEKamide, can modulate key functions of human neutrophils.
• These findings suggest that neurohormones, like enkephalins, play a role in regulating the peripheral immune response.
• The study supports the emerging concept of neurohormonal immunomodulation.