Enkephalins Modify Granulocyte-Endothelial Interactions by Stimulating Prostacyclin Production

Summary

Granulocyte (PMN)-endothehal interactions have been implicated in the primary events of vascular injury and atherogenesis. We now present data which show that endogenous opioid peptides, e.g. enkephalins (ENK), dampen immune-triggered, granulocyte-induced endothelial damage by enhancing prostacyclin production. Concurrent exposure of human umbilical vein endothelial cells (HUEC) to Met⁵5-enkephalin increased arachidonic acid (AA, 20 uM) and thrombin (T, 10 U/ml) induced 6-keto-PGF_1α-release to respectively 197.2 ± 28.1% and 204.1 ± 17.8% (mean ± SEM) of base line stimulation (p < 0.025). The increases noted were significant at ENK-concentrations as low as 10^-12M. Simultaneous addition of naloxone with ENK completely abolished the enhanced 6-keto-PGF_1α- release. Addition of a protease resistant enkephalin analogue significantly (p <0.01 over several different concentrations) reduced PMN adherence to HUEC; concomitantly ₅₁Cr-leakage from HUEC that had been exposed to PMN plus activated serum complement was decreased. The even further enhanced ⁵¹Cr- leakage that occurs when platelet release products (e.g. serotonin) are included is also decreased by added enkephalin. These data suggest that endogenous neurotransmitters may affect endothelial prostaglandin metabolism, and by so doing provide a protective effect during in vitro, and perhaps in vivo, PMN mediated endothelial injury. This link between neurohumoral and inflammatory systems might enhance our understanding of stress- related phenomena in inflammation and vascular diseases.

Keywords

Enkephalins - Prostacyclin - Granulocytes - Endothelial cells

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