Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.8 KDa), non-enzymatic basic protein which contains 3 disulfide bonds and a C-terminal rich in lysine. It is homologous to SALP14, a tick salivary FXa anticoagulant. Ixonnexin was produced by ligation of synthesized fragments (51-104) and (1-50) followed by folding. Ixonnexin, like SALP14, interacts with FXa. Notably, Ixonnexin also modulates fibrinolysis in vitro by a unique salivary mechanism. Accordingly, it accelerates plasminogen activation by tissue-type plasminogen activator (t-PA) with Km 100 nM; however, it does not affect urokinase-mediated fibrinolysis. Additionally, lysine analogue ε-aminocaproic acid inhibits Ixonnexin-mediated plasmin generation implying that lysine-binding sites of Kringle domain(s) of plasminogen or t-PA are involved in this process. Moreover, surface plasmon resonance experiments shows that Ixonnexin binds t-PA, and plasminogen (KD 10 nM), but not urokinase. These results imply that Ixonnexin promotes fibrinolysis by supporting the interaction of plasminogen with t-PA through formation of an enzymatically productive ternary complex. Finally, in vivo experiments demonstrates that Ixonnexin inhibits FeCl3-induced thrombosis in mice. Ixonnexin emerges as novel modulator of fibrinolysis which may also affect parasite-vector-host interactions.

• MeSH
• arteriální okluzní nemoci chemicky indukované   patologie   prevence a kontrola   MeSH
• chloridy toxicita   MeSH
• fibrinolýza účinky léků   MeSH
• klíšťata metabolismus   MeSH
• myši MeSH
• noxy toxicita   MeSH
• plazminogen metabolismus   MeSH
• slinné proteiny a peptidy farmakologie   MeSH
• sliny metabolismus   MeSH
• tkáňový aktivátor plazminogenu metabolismus   MeSH
• trombóza chemicky indukované   patologie   prevence a kontrola   MeSH
• železité sloučeniny toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH