Protease Inhibitor Eglin-C Affects Superoxide Anion Release but not Bacterial Killing by Human Polymorphonuclear Leukocytes

In order to assess the influence of the protease inhibitor eglin-c on superoxide anion (O−2) release by human polymorphonuclear leukocytes (PMN), cells were secured from normal donors and stimulated with phorbol myristate acetate (PMA), opsonized zymosan, or n-formyl-methionyl-leucyl-phenylalanine (FMLP). In the presence of 100 fxg/ml eglin-c, the activation time was prolonged and the maximum linear rate of O−2 formation was depressed following stimulation with PMA; a concentration of 1000 Hg/ml eglin-c was required to produce a similar effect with opsonized zymosan. Eglin-c did not influence the activation time following stimulation with FMLP, but at 2000 Hg/ml, the protease inhibitor attenuated the rate of O−2 production in response to the chemotactic peptide. In the presence of cytochalasin B, the inhibitory effect of eglin-c on O−2 release following stimulation with FMLP became more pronounced. In spite of these alterations in O−2 formation, the protease inhibitor did not impair the bactericidal activity of PMN against Staphylococcus aureus. Therefore, we conclude that although eglin-c can disrupt the activation and the activity of the superoxide-generating system of human PMN, the effect is stimulus dependent and is not associated with an alteration in the microbicidal capacity of neutrophils against S. aureus.