Modulation of human neutrophil function by endogenous opiate enkephalins

On the basis of recent evidence, the natural opiate enkephalins, which previously were believed to be confined to the central nervous system, are now known, in fact, to be released from the adrenal glands by sympathetic activation or trauma. To determine if enkephalins (EKs) affect peripheral function, the influence of synthetic leucine and methionine enkephalin (leuEK and metEK) on several relevant functions of human polymorphonuclear leukocytes was evaluated. Initial attempts to detect interaction of leuEK and metEK with neutrophils yielded inconsistent results. Further studies were done using protease-resistant methionine enkephalin-amide (metEKamide). MetEKamide was able to induce degranulation when present at 10(-3) and 10(-4) mmol/L as determined by release of beta-glucuronidase and lysozyme. Using the under-agarose chemotaxis method, treatment with metEKamide resulted in no change of the neutrophil's chemotactic response to an optimal concentration of the chemotactic peptide formyl-methionyl-leucyl-phenyl-alanine (FMLP). However, responsiveness to low levels of FMLP increased in cells treated with 10(-3)-10(-5) mmol/L metaEKamide. This appeared to be a result of increased chemokinesis of the treated cells. Scanning electron microscopic studies of cells exposed to metEKamide revealed that treatment resulted in changes in neutrophil morphology. When metEKamide itself was tested as a potential chemotactic agent, 10(-2) mmol/L metEKamide in an opposing well served to induce chemotaxis. Our results, along with those of recent studies of EKs as immunomodulators of T cell function, suggest that neurohormones can function as regulators of the immune response.