Antimicrobial peptide buforin I inhibits tissue factor-initiated coagulation.
The enhanced extrinsic blood coagulation following septic shock often manifests cardiovascular complications. The upregulated monocytic tissue factor (mTF) was shown to be a primary contributor to the extrinsic hypercoagulation following acute bacterial endotoxin (LPS) infection. A single-stage clotting assay monitors TF-initiated coagulation. We herein demonstrate a novel anticoagulant activity of antimicrobial peptide Buforin I (BF I) in offsetting LPS-induced mTF hypercoagulation in THP-1 cells, which was confirmed in a cell-free in vitro model, showing that BF I effectively blocked rabbit brain thromboplastin (rbTF) procoagulant activity. Upon inclusion of 25 microM BF I into human plasma, the prolonged prothrombin time (PT) was consistent with the depressed TF-initiated coagulation. In a two-stage chromogenic assay monitoring S-2288 hydrolysis, BF I significantly inhibited not only mTF- but also rbTF-catalyzed FVII activation accompanied by the diminished FVIIa formation. The inhibition by BF I of FVII activation accounted for its novel anticoagulant activity in offsetting mTF-initiated hypercoagulation.
Chu
A J
AJ
Department of Surgery, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA. ad5742@wayne.edu
Chen
B M
BM
Lin
H
H
Beydoun
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D002460:Cell Line; D005167:Factor VII / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D012772:Shock, Septic / Q000097:blood / Q000150:complications; D013925:Thromboplastin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology
D000890:Anti-Infective Agents; D008070:Lipopolysaccharides; D011506:Proteins; C097846:buforin I; D005167:Factor VII; D013925:Thromboplastin