ArticleArteriosclerosis, thrombosis, and vascular biology2012
Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Human sand fly challenge elicits saliva-specific innate and type 1-polarized immunity that promotes Leishmania killing.Communications biology · 2026Article
- Human sand fly challenge elicits saliva-specific innate and TbioRxiv : the preprint server for biology · 2025Article
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- PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes.Parasites & vectors · 2023Article
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- An overview of the sand fly salivary proteins in vaccine development against leishmaniases.Iranian journal of microbiology · 2022Review
- Alboserpin, the Main Salivary Anticoagulant from the Disease VectorImmunoHorizons · 2022Article
- Individuals co-exposed to sand fly saliva and filarial parasites exhibit altered monocyte function.PLoS neglected tropical diseases · 2021Article
- Engineering a vector-based pan-Leishmania vaccine for humans: proof of principle.Scientific reports · 2020Article
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- Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor.Nature immunology · 2018Article
- Ixonnexin from Tick Saliva Promotes Fibrinolysis by Interacting with Plasminogen and Tissue-Type Plasminogen Activator, and Prevents Arterial Thrombosis.Scientific reports · 2018Article
- Biomarkers for Zoonotic Visceral Leishmaniasis in Latin America.Frontiers in cellular and infection microbiology · 2018Review
- Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania.PLoS neglected tropical diseases · 2017Review
- The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B.Frontiers in immunology · 2017Article
- Role of the CD39/CD73 Purinergic Pathway in Modulating Arterial Thrombosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Molecular Diversity between Salivary Proteins from New World and Old World Sand Flies with Emphasis on Bichromomyia olmeca, the Sand Fly Vector of Leishmania mexicana in Mesoamerica.PLoS neglected tropical diseases · 2016Article
- SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.Scientific reports · 2016Article
- In Vitro Mode of Action and Anti-thrombotic Activity of Boophilin, a Multifunctional Kunitz Protease Inhibitor from the Midgut of a Tick Vector of Babesiosis, Rhipicephalus microplus.PLoS neglected tropical diseases · 2016Article
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Authors and funding
12 authors at 1 institution in 4 countries.
Funding
Abstract
objectiveBlood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. METHODS AND
resultsSeveral L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl(3)-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme.
conclusionsLufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.
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