Modulation of phagocytosis-associated respiratory burst by human cystatin C: role of the N-terminal tetrapeptide Lys-Pro-Pro-Arg.
Cystatin C, a cysteine protease inhibitor, has recently been suggested to be a potent regulator in inflammatory processes. Human cystatin C was isolated from the urine of one patient suffering from tubular disorders and was tested for its effects on two functions of human polymorphonuclear neutrophils (PMN): O2- release and phagocytosis. Slow-form or (des 1-4) cystatin C and fast-form or (des 1-8) cystatin C differed by the presence in (des 1-4) cystatin C only of the N-terminal tetrapeptide Lys-Pro-Pro-Arg. Whereas (des 1-8) cystatin C did not seem to interfere with PMN functions at physiological concentrations, (des 1-4) cystatin C induced an inhibition of PMN phagocytosis-associated respiratory burst in response to opsonized zymosan particles. The inhibition may be attributed to the tetrapeptide Lys-Pro-Pro-Arg which has been synthesized and shown to have the same inhibitor effects, at concentrations similar to those required for (des 1-4) cystatin C. These results support a potential role for cystatin C as a modulator during inflammation.
Leung-Tack
J
J
INSERM U 133, Faculté de Médecine, Toulouse, France.
Tavera
C
C
Gensac
M C
MC
Martinez
J
J
Colle
A
A
D000595:Amino Acid Sequence; D055316:Cystatin C; D015891:Cystatins / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects*; D010446:Peptide Fragments / Q000302:isolation & purification / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014405:Tuftsin / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D010446:Peptide Fragments; D010455:Peptides; C063740:cystatin C, N-terminal tetrapeptide; D013481:Superoxides; C063741:cystatin C, N-terminal octapeptide; D015054:Zymosan; D014405:Tuftsin