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Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors
Joint Authors
Svensjö, Erik
Nogueira de Almeida, Larissa
Vellasco, Lucas
Scharfstein, Julio
Juliano, Luiz
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-09-10
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Inhibitors of serine peptidases (ISPs) expressed by Leishmania major enhance intracellular parasitism in macrophages by targeting neutrophil elastase (NE), a serine protease that couples phagocytosis to the prooxidative TLR4/PKR pathway.
Here we investigated the functional interplay between ISP-expressing L.
major and the kallikrein-kinin system (KKS).
Enzymatic assays showed that NE inhibitor or recombinant ISP-2 inhibited KKS activation in human plasma activated by dextran sulfate.
Intravital microscopy in the hamster cheek pouch showed that topically applied L.
major promastigotes (WT and Δ i s p 2 / 3 mutants) potently induced plasma leakage through the activation of bradykinin B2 receptors (B2R).
Next, using mAbs against kininogen domains, we showed that these BK-precursor proteins are sequestered by L.
major promastigotes, being expressed at higher % in the Δ i s p 2 / 3 mutant population.
Strikingly, analysis of the role of kinin pathway in the phagocytic uptake of L.
major revealed that antagonists of B2R or B1R reversed the upregulated uptake of Δ i s p 2 / 3 mutants without inhibiting macrophage internalization of WT L.
major.
Collectively, our results suggest that L.
major ISP-2 fine-tunes macrophage phagocytosis by inhibiting the pericellular release of proinflammatory kinins from surface bound kininogens.
Ongoing studies should clarify whether L.
major ISP-2 subverts TLR4/PKR-dependent prooxidative responses of macrophages by preventing activation of G-protein coupled B2R/B1R.
American Psychological Association (APA)
Svensjö, Erik& Nogueira de Almeida, Larissa& Vellasco, Lucas& Juliano, Luiz& Scharfstein, Julio. 2014. Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors. Mediators of Inflammation،Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1043340
Modern Language Association (MLA)
Svensjö, Erik…[et al.]. Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors. Mediators of Inflammation No. 2014 (2014), pp.1-12.
https://search.emarefa.net/detail/BIM-1043340
American Medical Association (AMA)
Svensjö, Erik& Nogueira de Almeida, Larissa& Vellasco, Lucas& Juliano, Luiz& Scharfstein, Julio. Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors. Mediators of Inflammation. 2014. Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1043340
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1043340