Hypotensive proteins from hematophagous animals

Abstract

Diverse arthropods exploit vertebrate blood as a food resource, despite the fact that this resource is defended by an array of haemostatic, inflammatory, and immune responses, as well as overt defensive behaviors. These defenses have selected for a broad array of antihaemostatic, anti-inflammatory, and immunomodulatory factors, which are secreted in the saliva of the blood-feeder and injected into the wound during the feeding process. Haemostasis includes three interacting branches: platelet activation and aggregation, vasoconstriction, and coagulation (or clotting). This review deals with salivary factors that counter the vasoconstriction that normally results following vascular injury, but as the branches of haemostasis overlap, and indeed haemostasis interacts with inflammation and immunity, some molecules with vasodilatory (hypotensive) activity may also affect other aspects of the vertebrate response, in which case they are also discussed. Blood-feeding has evolved on numerous independent occasions, leading to a wide diversity of molecules with hypotensive activity amongst extant arthropods. These molecules exploit mechanisms that include direct interaction with vertebrate receptors or signaling pathways leading to vasodilation, sequestration of endogenously generated vasoconstrictors, and enzymatic destruction of vasoconstrictors. Some vasodilators, specifically the nitrophorins from Rhodnius and Cimex, allow the arthropod to store physiological amounts of nitric oxide and secrete it into the bite site during the course of the blood meal. Finally, several instances are noted where arthropod saliva is known to contain hypotensive activity, but the molecules involved have not been identified.