Reciprocal effects between opioid peptides and human polymorphonuclear leukocytes--I. Chemical modifications of Leu-enkephalin by phorbol myristate acetate-stimulated polymorphonuclear leukocytes.

When L-tyrosyl-glycyl-L-phenylalanyl-L-leucine (Leu-enkephalin) is exposed to the activated oxygen species produced by phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocytes (PMNs), hydroxylation of the phenylalanyl residue in position 4 of the peptide occurs, producing hydroxy-phenylalanyl derivatives which are identified by HPLC analysis and mass spectrometry. Attack of hydroxyl radicals generated by the Cu (II)/ascorbate system upon Leu-enkephalin also produces isomeric o-, m- and p-hydroxy-phenylalanyl derivatives. When PMNs are incubated with a synthetic peptide, L-tyrosyl-glycyl-glycyl-L-tyrosyl-L-leucine used as a model of hydroxylated Leu-enkephalin, their chemiluminescence response to PMA activation is higher than that of PMNs incubated with Leu-enkephalin.