Inhibition of neutrophil derived lysosomal enzymes and reactive oxygen species by a novel tetrapeptide.

Abstract

The role of a tetrapeptide derivative PEP 1261 {Boc-Lys(Boc)-Arg-Asp-Ser(tBu)-OtBu}, corresponding to residues 39-42 of human lactoferrin, has been tested in vitro in the modulation of neutrophil function. The level of non-enzymatic mediators of inflammation such as reactive oxygen species (ROS), enzymatic mediators such as myeloperoxidase (MPO) and lysosomal enzymes have been assessed in the presence or absence of PEP 1261 in phorbol 12-myristate 13 acetate (PMA) stimulated human neutrophils (n = 6) and also in neutrophils isolated from adjuvant induced arthritic rats (AIA) (n = 4). PEP 1261, at a concentration of 0.14 mM, was added to the neutrophil cultures. The results were analysed by nonparametric statistics using Mann Whitney U test. Addition of PEP 1261 effectively blocked the H2O2 and O2*- release, decreased the levels of MPO levels (p< 0.01) and lysosomal enzymes (p < 0.05) as compared to PMA stimulated human neutrophils. PEP 1261 was also observed to inhibit the levels of H2O2, O2*-, MPO and lysosomal enzymes (p < 0.05) as compared to PMA stimulated control rat neutrophils and neutrophils from arthritic rats. The results of this study indicate that PEP 1261 could serve as an excellent antiinflammatory agent.