title: Anti-hemostatic effects of a serpin from the saliva of the tick Ixodes ricinus.
abstract: Serpins (serine protease inhibitors) are a large family of structurally related proteins found in a wide variety of organisms, including hematophagous arthropods. Protein analyses revealed that Iris, previously described as an immunomodulator secreted in the tick saliva, is related to the leukocyte elastase inhibitor and possesses serpin motifs, including the reactive center loop (RCL), which is involved in the interaction between serpins and serine proteases. Only serine proteases were inhibited by purified recombinant Iris (rIris), whereas mutants L339A and A332P were found devoid of any protease inhibitory activity. The highest Ka was observed with human leukocyte-elastase, suggesting that elastase-like proteases are the natural targets of Iris. In addition, mutation M340R completely changed both Iris substrate specificity and affinity. This likely identified Met-340 as amino acid P1 in the RCL. The effects of rIris and its mutants were also tested on primary hemostasis, blood clotting, and fibrinolysis. rIris increased platelet adhesion, the contact phase-activated pathway of coagulation, and fibrinolysis times in a dose-dependent manner, whereas rIris mutant L339A affected only platelet adhesion. Taken together, these results indicate that Iris disrupts coagulation and fibrinolysis via the anti-proteolytic RCL domain. One or more other domains could be responsible for primary hemostasis inhibition. To our knowledge, this is the first ectoparasite serpin that interferes with both hemostasis and the immune response.
authors: Department of Génétique Appliquée, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet, 12, B-6041 Gosselies, Belgium.
authors: Pierre-Paul
authors: PP
authors: Prevot
authors: Benoit
authors: B
authors: Adam
authors: Karim Zouaoui
authors: KZ
authors: Boudjeltia
authors: Michel
authors: M
authors: Brossard
authors: Laurence
authors: L
authors: Lins
authors: Philippe
authors: P
authors: Cauchie
authors: Robert
authors: R
authors: Brasseur
authors: Michel
authors: M
authors: Vanhaeverbeek
authors: Luc
authors: L
authors: Vanhamme
authors: Edmond
authors: E
authors: Godfroid