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 micrograms/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 micrograms/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 micrograms/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.
Esposito
A L
AL
Department of Medicine, Boston University Medical Center, Massachusetts.
Clark
C A
CA
Poirier
W J
WJ
Kephart
P A
PA
D000838:Anions / Q000378:metabolism; D001770:Blood Bactericidal Activity / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010586:Phagocytes / Q000187:drug effects / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D015843:Serpins; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
D000838:Anions; D011480:Protease Inhibitors; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D013481:Superoxides