Hirudin C-terminal fragments inhibit thrombin induced neutrophil chemotaxis.
Since native hirudin blocks the thrombin induced chemotaxis response of neutrophils, we examined whether hirudin C-terminal peptides were also capable of this inhibition. The studies showed that thrombin induced human neutrophil chemotaxis was effectively blocked by the C-terminal hirudin peptide analogs, Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gln (12-mer[54-65]) and Thr-Pro-Lys-Pro-Gln-Ser-His-Asn-Asp-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu- Tyr- Leu-Gln (21-mer[45-65]). Furthermore, neither peptide had an effect on formyl-L-methionyl-L-leucyl-L-phenylalanine induced chemotaxis. The results suggest that binding of the hirudin C-terminal peptides block the thrombin chemotactic domain.
Rowand
J K
JK
Department of Chemistry, Ohio State University, Columbus 43210-1173.
Marucha
P
P
Berliner
L J
LJ
D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006629:Hirudins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors*
D006629:Hirudins; D010446:Peptide Fragments; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013917:Thrombin