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

  • Immunohorizons. 2022 Jun 23;6(6):373-383. doi: 10.4049/immunohorizons.2200045.
Gaurav Shrivastava  1 ,  Paola Carolina Valenzuela-Leon  1 ,  Andrezza Campos Chagas  1 ,  Olivia Kern  1 ,  Karina Botello  1 ,  Yixiang Zhang  2 ,  Ines Martin-Martin  1 ,  Markus Berger Oliveira  3 ,  Lucas Tirloni  3 ,  Eric Calvo  4
Affiliations
  • 1. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD.
  • 2. Protein Chemistry Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT; and.
  • 3. Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, MT.
  • 4. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD; [email protected].
PMID: 35738824 DOI: 10.4049/immunohorizons.2200045
Abstract

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 Aedes albopictus, 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.