Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis.
We have recently provided evidence that C-reactive protein (CRP) could act as an up-regulatable substrate for membrane-associated neutrophil serine protease(s). The resultant degradation of CRP yielded small soluble bioactive peptides that inhibit many of the proinflammatory functions of activated neutrophils and could oppose the tissue destructive potential of these cells. We report on the reverse phase HPLC separation of the small TCA-soluble peptides obtained when CRP is degraded with nonstimulated or PMA-stimulated neutrophils and purified neutrophil membranes. The amino acid sequence of seven peptides isolated from the CRP digest has been ascertained and synthetic peptides homologous to these sequences have been synthesized. Three of the synthetic peptides corresponding to residues 201-206 (CRP-III), 83-90 (CRP-IV), and 77-82 (CRP-V) of the intact protein were identified to significantly inhibit superoxide production from activated neutrophils at 50 microM whereas CRP-III and CRP-V in addition inhibited neutrophil chemotaxis at this concentration. These peptides act additively and their action likely involves the signal transduction pathways for neutrophil activation.
Shephard
E G
EG
Department of Internal Medicine, Faculty of Medicine, University of Stellenbosch.
Anderson
R
R
Rosen
O
O
Myer
M S
MS
Fridkin
M
M
Strachan
A F
AF
De Beer
F C
FC
D000595:Amino Acid Sequence; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002097:C-Reactive Protein / Q000032:analysis* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002634:Chemotaxis, Leukocyte; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D010446:Peptide Fragments; D013481:Superoxides; D016718:Arachidonic Acid; D002097:C-Reactive Protein; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D002118:Calcium