Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo

• Published in: ImmunoHorizons 2022-06, Vol.6 (6), p.373-383
• Main Authors: Shrivastava, Gaurav, Valenzuela-Leon, Paola Carolina, Chagas, Andrezza Campos, Kern, Olivia, Botello, Karina, Zhang, Yixiang, Martin-Martin, Ines, Oliveira, Markus Berger, Tirloni, Lucas, Calvo, Eric
• Format: Article
• Language: English
• Subjects: Aedes - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; Anticoagulants - pharmacology; Cytokines; Endothelial Cells - metabolism; Humans; Interleukin-6; Mosquito Vectors; Receptor, PAR-1 - genetics; Receptor, PAR-1 - metabolism
• ISSN: 2573-7732; 2573-7732
• DOI: 10.4049/immunohorizons.2200045

Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector , is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding.