Neutrophil chemotactic activity is modulated by human cystatin C, an inhibitor of cysteine proteases.
Cystatin C, a cysteine proteinase inhibitor has recently been suggested to be a potent regulator of inflammatory processes and may act in defense against viral and bacterial infections. Two common forms of the protein were purified from the urine of a patient having received a renal transplant. The slow form of cystatin C possessed the N-terminal tetrapeptide Lys Pro Pro Arg, which was cleaved in the fast form. This peptide sequence, called postin, was synthesized. The three molecules, slow and fast forms of cystatin and the synthetic peptide, were tested for their effects on the migration activity of human polymorphonuclear neutrophils (PMNs). The slow form was found to display both chemotactic and chemokinetic activities, while the fast form and postin were only chemokinetic. Nevertheless, all the substances could induce a "motile" morphology. In addition, the two forms of cystatin C were powerful inhibitors of PMN chemotaxis induced by complement-derived chemotactic factors. This suggests that cystatin C in its two different cleaved forms and the N-terminal tetrapeptide can modulate PMN locomotion. Cysteine proteases may therefore play a role in neutrophil migration activity.
Leung-Tack
J
J
INSERM U 133, Faculté de Médecine, Toulouse, France.
Tavera
C
C
Martinez
J
J
Colle
A
A
D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D055316:Cystatin C; D015891:Cystatins / Q000138:chemical synthesis / Q000145:classification / Q000302:isolation & purification / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D003864:Depression, Chemical; D006801:Humans; D016030:Kidney Transplantation; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D010446:Peptide Fragments; C063740:cystatin C, N-terminal tetrapeptide