Summary
For centuries, maggots have been used for the treatment of wounds by a variety of
ancient cultures, as part of their traditional medicine. With increasing appearance
of antimicrobial resistance and in association with diabetic ulcers, maggot therapy
was revisited in the 1980s. Three mechanisms by which sterile maggots of the green
bottle fly Lucilia sericata may improve healing of chronic wounds have been proposed: Biosurgical debridement,
disinfecting properties, and stimulation of the wound healing process. However, the
influence of maggot excretion products (MEP) on blood coagulation as part of the wound
healing process has not been studied in detail. Here, we demonstrate that specific
MEP-derived serine proteases from Lucilia sericata induce clotting of human plasma and whole blood, particularly by activating contact
phase proteins factor XII and kininogen as well as factor IX, thereby providing kallikrein-bypassing
and factor XIa-like activities, both in plasma and in isolated systems. In plasma
samples deficient in contact phase proteins, MEP restored full clotting activity,
whereas in plasma deficient in either factor VII, IX, X or II no effect was seen.
The observed procoagulant/intrinsic pathway-like activity was mediated by (chymo-)
trypsin-like proteases in total MEP, which were significantly blocked by C1-esterase
inhibitor or other contact phase-specific protease inhibitors. No significant influence
of MEP on platelet activation or fibrinolysis was noted. Together, MEP provides contact
phase bypassing procoagulant activity and thereby induces blood clotting in the context
of wound healing. Further characterisation of the active serine protease(s) may offer
new perspectives for biosurgical treatment of chronic wounds.
Keywords
Maggot therapy -
Lucilia sericata
- wound repair - blood coagulation - contact phase proteins
