Hematophagous Organisms Research Articles

Extracellular lipid droplets promote hemozoin crystallization in the gut of the blood fluke Schistosoma mansoni

Hemozoin (Hz) is a heme crystal produced upon hemoglobin digestion as the main mechanism of heme disposal in several hematophagous organisms. Here, we show that, in the helminth Schistosoma mansoni, Hz formation occurs in extracellular lipid droplets (LDs). Transmission electron microscopy of adult worms revealed the presence of numerous electron-lucent round structures similar to LDs in gut lumen, where multicrystalline Hz assemblies were found associated to their surfaces. Female regurgitates promoted Hz formation in vitro in reactions partially inhibited by boiling. Fractionation of regurgitates showed that Hz crystallization activity was essentially concentrated on lower density fractions, which have small amounts of pre-formed Hz crystals, suggesting that hydrophilic–hydrophobic interfaces, and not Hz itself, play a key catalytic role in Hz formation in S. mansoni. Thus, these data demonstrate that LDs present in the gut lumen of S. mansoni support Hz formation possibly by allowing association of heme to the lipid–water interface of these structures.

Beyond heparin and warfarin: the new generation of anticoagulants

Heparin and warfarin are widely used for the prevention and treatment of venous and arterial thromboembolism. Although effective, both agents have important limitations; for example, both drugs must be monitored, which is inconvenient for patients and for physicians. Heparin requires parenteral administration and can cause heparin-induced thrombocytopenia, an immune-mediated process that can lead to life-threatening thrombosis. Warfarin also has its limitations. Due to its slow onset of action, warfarin must be overlapped with heparin (or another rapidly acting anticoagulant) when treating patients with established thrombosis or who are at high risk for thrombosis. Warfarin dosing is variable because its activity is influenced by dietary intake of vitamin K, genetic polymorphisms in enzymes that are involved in its metabolism and numerous drug–drug interactions that promote or reduce its activity. New anticoagulants have been developed to overcome these problems. Building on a better understanding of coagulation pathways, advances in structure-based drug design and information derived from natural anticoagulants isolated from hematophagous organisms, most of the new anticoagulants target specific coagulation enzymes. Focussing on drugs that have at least completed Phase II evaluation, this article briefly reviews the coagulation pathways and its natural regulators; outlines the limitations of existing anticoagulants and identifies the opportunities for new ones; highlights the properties of selected new anticoagulants; describes the clinical trial results with these agents; and provides a perspective on their potential strengths and weaknesses.

Adaptations against heme toxicity in blood-feeding arthropods

A blood-sucking habit appeared independently several times in the course of arthropod evolution. However, from more than a million species of insects and arachnids presently living on earth, only about 14,000 species developed the capacity to feed on vertebrate blood. This figure suggests the existence of severe physiological constraints for the evolution of hematophagy, implying the selective advantage of special adaptations related to the use of blood as a food source. Digestion of vertebrate hemoglobin in the midgut of blood-feeding arthropods results in the production of large amounts of heme, a potentially cytotoxic molecule. Here we will review mechanisms by which heme can exert biological damage, together with a wide spectrum of adaptations developed by blood-feeding insects and ticks to counteract its deleterious effects. In spite of the existence of a great molecular diversity of protective mechanisms, different hematophagous organisms developed convergent solutions that may be physiologically equivalent.

Spleen accessory cell antigen processing and in vitro induction of specific lymphocyte proliferation in BALB/c mice infested with nymphal Ixodes ricinus ticks.

Ticks are hematophagous organisms that transmit numerous human and veterinary diseases. They also induce an anti tick immune response during their blood meal. Thus, rabbits repeatedly infested with I. ricinus nymphs and adults produce IgG antibodies reacting against some salivary gland and integumental proteins from female ticks1. In contrast, experimental infestations of BALB/c mice with nymphal I. ricinus do not generate anti tick antibodies (IgG) or only occasionally. However mice immunized with salivary gland extract (SGE) develop antibodies that recognize tick integumental and salivary gland proteins (Fig 1).KeywordsSalivary GlandBlood MealAntigen ProcessingTritiated ThymidineFemale TickThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.