Bee venom contains serine proteases and serine protease inhibitors. In this study, we identified a bumblebee (Bombus ignitus) venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent. The fibrin(ogen)olytic activities of B. ignitus venom serine protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel mechanism by which bumblebee venom affects the hemostatic system through the antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated fibrin(ogen) olytic activities, raising interest in Bi-KTI and Bi-VSP as potential clinical agents.

• Kwang Sik Lee(College of Natural Resources and Life Science, Dong-A University)
• Young Moo Choo(College of Natural Resources and Life Science, Dong-A University)
• Hyung Joo Yoon(Department of Agricultural Biology, National Academy of Agricultural Science)
• Byung Rae Jin(College of Natural Resources and Life Science, Dong-A University)