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

Objective and Design: The role of a tetrapeptide derivative PEP 1261 {Boc-L ys(Boc)-Arg-Asp-Ser(tBu)-OtBu}, corresponding to residues 39-42 of human la ctoferrin, has been tested in vitro in the modulation of neutrophil functio n. Material and Subjects: The level of non-enzymatic mediators of inflammation such as reactive oxygen species (ROS), enzymatic mediators such as myelope roxidase (MPO) and lysosomal enzymes have been assessed in the presence or absence of PEP 1261 in phorbol 12-myristate 13 acetate (PMA) stimulated hum an neutrophils (n = 6) and also in neutrophils isolated from adjuvant induc ed arthritic rats (AIA) (n = 4). Treatment: PEP 1261, at a concentration of 0.14 mM, was added to the neutro phil cultures. Statistical Method: The results were analysed by nonparametric statistics u sing Mann Whitney U test. Results: Addition of PEP 1261 effectively blocked the H2O2 and O-2(.-) rele ase, 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, O-2(.-), MPO and lysosomal enzymes (p < 0.05) as compared to PMA stimulated control rat neutrophils and neutr ophils from arthritic rats. Conclusions: The results of this study indicate that PEP 1261 could serve a s an excellent antiinflammatory agent.