title: A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis.
abstract: 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.
authors.affiliation: Department of Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariena J A
authors.initials: MJ
authors.lastname: van der Plas
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institute, Copenhagen, Denmark; Novozymes A/S, Bagsvaerd, Denmark; Copenhagen Wound Healing Center, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Andersen
authors.affiliation: Department of Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sheresma
authors.initials: S
authors.lastname: Nazir
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nico H
authors.initials: NH
authors.lastname: van Tilburg
authors.affiliation: Novozymes A/S, Bagsvaerd, Denmark.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Oestergaard
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt
authors.affiliation: Department of Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hensbergen
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
authors.affiliation: Department of Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D004175:Diptera / Q000187:drug effects / Q000201:enzymology*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007814:Larva; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000494:pharmacology*; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
chemical_list: D010958:Plasminogen; D057057:Serine Proteases; D010960:Plasminogen Activators; D005341:Fibrinolysin