Antihemostatic Molecules from Saliva of Blood-Feeding Arthropods

Abstract

The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Each time this trait evolves, novel solutions to the problem posed by vertebrate hemostasis are generated. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Molecular approaches (termed ‘sialomics’) to characterize the full inventory of mRNAs transcribed in salivary glands have revealed a surprising level of complexity within a single species. Multiple salivary proteins may be directed against each component of hemostasis, resulting in both redundancy and in some cases cooperative interactions between antihemostatic proteins, as in the case of the Rhodnius prolixus apyrase (which hydrolyzes ADP) and Rhodnius platelet aggregation inhibitor 1 (which sequesters ADP). The complexity and redundancy of saliva ensures an efficient blood meal for the arthropod, but it also provides a diverse array of novel antihemostatic molecules for the pharmacologist.

Protective immunity against Ixodes ricinus induced by a salivary serpin

“…In parallel, ticks have developed countermeasures such as salivary proteins able to inhibit one or both processes [8,27,[36][37][38][39]. These mechanisms are obviously good targets for vaccination.…”

Anticoagulant activity in salivary gland homogenates of Thyrsopelma guianense (Diptera: Simuliidae), the primary vector of onchocerciasis in the Brazilian Amazon

“…New compounds arose which allowed these organisms to avoid the hemostasis of the vertebrate host, making the saliva a rich source of antihemostatic molecules (Ribeiro & Francischetti 2003, Champagne 2004, 2005. These include a great diversity of vasodilators (Lerner et al 1991, Law et al 1992, Champagne & Ribeiro 1994, inhibitors of platelet aggregation (Cupp et al 1993, 1995, Moreira-Ferro et al 1999, Valenzuela et al 2001) and inhibitors of blood coagulation (Jacobs et al 1990, Abebe et al 1995, Capello et al 1996, Stark & James 1998, Valenzuela et al 1999, Cupp et al 2000, Horn et al 2000, Zang et al 2002.…”

Variegin, a Novel Fast and Tight Binding Thrombin Inhibitor from the Tropical Bont Tick

“…Over the last few hundred million years, hematophagous arthropods have evolved a rich reservoir of inhibitors for blood coagulation proteases (16,17). The success of hirudin and bivalirudin demonstrated the feasibility of identifying and developing such anticoagulants.…”