Available Technology

N-Formyl Peptide Receptor Mediation of Platelet Chemotaxis Toward Injured Cells and Activation of Immune Response

Formyl peptides are short peptides generated by bacterial or mitochondrial endopepdidase cleavage of the first few amino acids including the N-formyl-modified methionine group of proteins. They bind to specific receptors on phagocytic cells and platelets, and induce directed migration or chemotaxis. Human phagocytes express two N-formyl peptide receptors, FPR (N-formyl peptide receptor) and FPRL-1 (FPR-like 1), both of which couple to pertussis toxin-sensitive G proteins. FPR binds N-formyl peptides at a 1000 fold higher affinity than FPRL 1 and is attributed with inducing chemotaxis. Based on their chemotactic actions, it has been hypothesized that N-formyl peptides attract phagocytes and platelets to sites of infection and injury and therefore play an important role in microbicidal and other host defense activities. In particular, platelets carry CD154 or CD40 ligand on their surface and can provide induction of dendritic cell maturation and co-stimulatory molecule expression, thus regulating immune versus tolerance responses. Claimed in the invention are compositions of N-formyl peptides and derivatives of N-formal peptides, use of N-formyl peptides to stimulate an immune or inflammatory response, and methods of using N-formal peptide receptor inhibitors, such as blocking antibodies or other receptor antagonists, for inhibiting inflammation. Also claimed in the invention are methods of mobilizing platelets at an injury site and methods of wound healing at an injury site comprising administering N-formal peptides to the site.
Inventors: 

David Kleiner

Allan Kirk (NIDDK)

Internal Laboratory Ref #: 
E-282-2001/0
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