Boomerang effect between [Met]-enkephalin derivatives and human polymorphonuclear leukocytes

[Met]-enkephalin or its precursor, pre-[Met]-enkephalin, were exposed to activated oxygen species produced by human phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocytes (PMNs) and then analyzed by high-pressure liquid chromatography (HPLC). The chromatograms recorded at the tyrosine maximum wavelength (lambda em 300 nm and lambda ex 280 nm) showed the formation of new peptides by oxidation of methionyl residue in position 5 and ortho, meta, or para hydroxylation of phenylalanyl residue in position 4. The chromatograms recorded at the dityrosine maximum wavelength (lambda em 400 nm and lambda ex 325 nm) showed the formation of new dimeric peptides which contained two [Met]-enkephalin-derivatives linked by a dityrosyl group. These new peptides were tested for chemiluminescence response to PMA-stimulated PMNs. [Met]-enkephalin, pre-[Met]-enkephalin, and the methionyl-oxidized derivatives suppressed the PMA-induced respiratory burst of PMNs. Conversely, after hydroxylation by activated oxygen species released by stimulated PMNs, these peptides enhanced the PMA-induced respiratory burst of PMNs. In the same conditions, dimeric peptides had no effect.