A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis

TY - JOUR

T1 - A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis

AU - van der Plas, Mariena J A

AU - Andersen, Anders S

AU - Nazir, Sheresma

AU - van Tilburg, Nico H

AU - Oestergaard, Peter R

AU - Krogfelt, Karen A

AU - van Dissel, Jaap T

AU - Hensbergen, Paul J

AU - Bertina, Rogier M

AU - Nibbering, Peter H

PY - 2014/3/19

Y1 - 2014/3/19

N2 - Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasminogen activator-induced formation of plasmin and fibrinolysis in a dose- and time-dependent manner. By contrast, coagulation was not affected by secretions. Biochemical studies indicated that a novel serine protease within secretions, designated Sericase, cleaved plasminogen to several fragments. Recombinant Sericase degraded plasminogen leading amongst others to the formation of the mini-plasminogen like fragment Val454-plasminogen. In addition, the presence of a non-proteolytic cofactor in secretions was discovered, which plays a role in the enhancement of plasminogen activator-induced fibrinolysis by Sericase. We conclude from our in vitro studies that the novel serine protease Sericase, with the aid of a non-proteolytic cofactor, enhances plasminogen activator-induced fibrinolysis.

AB - Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasminogen activator-induced formation of plasmin and fibrinolysis in a dose- and time-dependent manner. By contrast, coagulation was not affected by secretions. Biochemical studies indicated that a novel serine protease within secretions, designated Sericase, cleaved plasminogen to several fragments. Recombinant Sericase degraded plasminogen leading amongst others to the formation of the mini-plasminogen like fragment Val454-plasminogen. In addition, the presence of a non-proteolytic cofactor in secretions was discovered, which plays a role in the enhancement of plasminogen activator-induced fibrinolysis by Sericase. We conclude from our in vitro studies that the novel serine protease Sericase, with the aid of a non-proteolytic cofactor, enhances plasminogen activator-induced fibrinolysis.

KW - Amino Acid Sequence

KW - Animals

KW - Blood Coagulation

KW - Diptera

KW - Fibrinolysin

KW - Fibrinolysis

KW - Humans

KW - Larva

KW - Molecular Sequence Data

KW - Plasminogen

KW - Plasminogen Activators

KW - Serine Proteases

KW - Time Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0092096

DO - 10.1371/journal.pone.0092096

M3 - Journal article

C2 - 24647546

SN - 1932-6203

VL - 9

SP - e92096

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 3

ER -