title: Influence of tuftsin-like synthetic peptides derived from C-reactive protein (CRP) on platelet behaviour.
abstract: C-reactive protein (CRP) is an acute-phase reactant that modifies platelet function differently, depending upon its physiochemical state. Aggregated and ligand-complexed forms of CRP initiate the activation of platelets, whereas naturally occurring CRP peptides inhibit platelet activation. The present study documents neutral proteases of the polymorphonuclear leucocyte (PMN) to cleave CRP into reaction products with the potential to inhibit platelet activation, and explore the structure-function relationships involved in the regulation of platelet activation by CRP using synthetic CRP peptides. Evidence was obtained that (i) a minimum of two linear functional domains exist within CRP that influence platelet activation; (ii) they reside in the mid-portion and at the C-terminus of the CRP molecule; (iii) the mid-portion domain inhibits platelet activation stimulated by adenosine diphosphate (ADP) or acid-soluble collagen, whereas the C-terminal domain initiates platelet activation; (iv) the functional expression of the C-terminal domain is maximized when the linear peptide is immobilized on latex; and (v) both CRP domains contain a homologue of the immunoregulatory signal peptide, tuftsin. These data suggest that the molecular mechanisms by which platelet processes are modulated by CRP may be related to the presence of tuftsin homologues in CRP.
mesh_terms: D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects*; D002097:C-Reactive Protein / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014405:Tuftsin / Q000494:pharmacology*
chemical_list: D010455:Peptides; D002097:C-Reactive Protein; D010447:Peptide Hydrolases; D014405:Tuftsin