CASEIN-DERIVED PEPTIDES CAN MODULATE THE PRODUCTION OF 5-HYDROXYEICOSATETRAENOIC ACID IN HUMAN NEUTROPHILS

The effects of peptides derived from bovine casein hydrolysates were e valuated on oxygen-free radical release, 5-hydroxyeicosatetraenoic aci d (5-HETE), and leukotriene B-4 (LTB(4)) production by human polymorph onuclear leukocytes (PMNs). PMNs were activated by N-formyl-methionyl- leucyl-phenylalanine, phorbol myristate acetate, calcium ionophore (A2 3187), or opsonized zymosan. Tyrosyl-prolyl-phenylalanyl-proline (frag ment 60-63 from bovine beta-casein) inhibited oxygen-free radical prod uction and 5-HETE production but had no effect on the production of LT B(4) and LTB(4) isomers. Arginyl-tyrosyl-leucyl-glycyl-tyrosyl-leucine (fragment 90-95 from bovine alpha-casein) enhanced the production of oxygen-free radical and 5-HETE but had no effect on the production of LTB(4) and isomers. Both peptides unsignificantly enhanced the release of arachidonic acid by A23187-stimulated PMNs previously supplemented with [C-14]arachidonic acid. Casein-derived peptides then seemed to a ct on the enzymatic activities of endogenous peroxidases that reduced hydroperoxyeicosatetraenoic acid to 5-HETE. 5-HETE is recognized as an ubiquitous cell function mediator and modulation of PMN 5-HETE produc tion by casein-derived peptides could be implicated in the manifestati on of some adverse effects to cow's milk.