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Exosites mediate the anti‐inflammatory effects of a multifunctional serpin from the saliva of the tick Ixodes ricinus
Author(s) -
Prevot PierrePaul,
Beschin Alain,
Lins Laurence,
Beaufays Jérôme,
Grosjean Amélie,
Bruys Léa,
Adam Benoît,
Brossard Michel,
Brasseur Robert,
Zouaoui Boudjeltia Karim,
Vanhamme Luc,
Godfroid Edmond
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07038.x
Subject(s) - serpin , biology , coagulation , serine protease , tumor necrosis factor alpha , fibrinolysis , immunology , microbiology and biotechnology , protease , biochemistry , medicine , psychiatry , gene , enzyme
Serine protease inhibitors (serpins) are a structurally related but functionally diverse family of ubiquitous proteins. We previously described Ixodes ricinus immunosuppressor (Iris) as a serpin from the saliva of the tick I. ricinus displaying high affinity for human leukocyte elastase. Iris also displays pleotropic effects because it interferes with both the immune response and hemostasis of the host. It thus inhibits lymphocyte proliferation and the secretion of interferon‐γ or tumor necrosis factor‐α by peripheral blood mononuclear cells, and also platelet adhesion, coagulation and fibrinolysis. Its ability to interfere with coagulation and fibrinolysis, but not platelet adhesion, depends on the integrity of its antiproteolytic reactive center loop domain. Here, we dissect the mechanisms underlying the interaction of recombinant Iris with peripheral blood mononuclear cells. We show that Iris binds to monocytes/macrophages and inhibits their ability to secrete tumor necrosis factor‐α. Recombinant Iris also has a protective role in endotoxemic shock. The anti‐inflammatory ability of Iris does not depend on its antiprotease activity. Moreover, we pinpoint the exosites involved in this activity.