Effects of Tsetse (Glossina morsitans morsitans Westw.) (Diptera: Glossinidae) Salivary Gland Homogenate on Coagulation and Fibrinolysis

Parker, Kenneth; Mant, Michael J.

doi:10.1055/s-0038-1666912

Cited by 30 publications

(13 citation statements)

References 11 publications

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“…However, it was not until 1966 that Hawkins (8) determined that all of the anticoagulant activity present in salivary extracts of Glossina austeni could be attributed to the inhibition of thrombin, the terminal protease in the mammalian coagulation cascade. A similar antithrombin activity was later identified in G. morsitans (9), and in 1996 we reported the purification and characterization of this low molecular weight anticoagulant, which we named the tsetse thrombin inhibitor (TTI) (10). In addition to its small size (3,530 Da), TTI is one of the most potent (K i * ϭ 584 fM) naturally occurring anticoagulants ever identified, with remarkable specificity for thrombin.…”

Section: Discussionmentioning

confidence: 67%

“…These bloodfeeding insects have been known for decades to produce a potent salivary anticoagulant (6). First characterized as an ''antikinase'' (7), this activity was ultimately identified as an inhibitor of thrombin (8,9). Recently, the tsetse thrombin inhibitor (TTI), a potent (K i * ϭ 584 fM) 32-aa peptide, was purified to homogeneity from salivary gland extracts of Glossina morsitans morsitans (10).…”

Section: Introductionmentioning

confidence: 99%

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Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans

Cappello

Chen

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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The tsetse thrombin inhibitor, a potent and specific low molecular mass (3,530 Da) anticoagulant peptide, was purified previously from salivary gland extracts of Glossina morsitans morsitans (Diptera: Glossinidae). A 303-bp coding sequence corresponding to the inhibitor has now been isolated from a tsetse salivary gland cDNA library by using degenerate oligonucleotide probes. The full-length cDNA contains a 26-bp untranslated segment at its 5 end, followed by a 63-bp sequence corresponding to a putative secretory signal peptide. A 96-bp segment codes for the mature tsetse thrombin inhibitor, whose predicted molecular weight matches that of the purified native protein. Based on its lack of homology to any previously described family of molecules, the tsetse thrombin inhibitor appears to represent a unique class of naturally occurring protease inhibitors. Recombinant tsetse thrombin inhibitor expressed in Escherichia coli and the chemically synthesized peptide are both substantially less active than the purified native protein, suggesting that posttranslational modification(s) may be necessary for optimal inhibitory activity. The tsetse thrombin inhibitor gene, which is present as a single copy in the tsetse genome, is expressed at high levels in salivary glands and midguts of adult tsetse flies, suggesting a possible role for the anticoagulant in both feeding and processing of the bloodmeal.The saliva of hematophagous invertebrates contains a diverse array of potent antithrombotic molecules, including anticoagulants, vasodilators, and inhibitors of platelet function (1-3). In the case of certain ''pool-feeding'' insects, particularly biting flies, these antihemostatic agents are thought to facilitate the rapid formation of a subcutaneous hematoma, from which the insect can suck blood efficiently. By inhibiting the critical steps through which the mammalian thrombotic response limits blood loss at the site of tissue damage, these insects are able to feed quickly, often requiring only seconds to complete their meal. It is during feeding that many of these arthropods also transmit important infectious pathogens, including protozoa, nematodes, and viruses, which are injected into or deposited on the skin as the insect probes for blood (4, 5).Tsetse flies (Diptera: Glossinidae) are the invertebrate hosts of African trypanosomes, protozoan parasites that cause sleeping sickness in humans and related diseases in cattle. These bloodfeeding insects have been known for decades to produce a potent salivary anticoagulant (6). First characterized as an ''antikinase'' (7), this activity was ultimately identified as an inhibitor of thrombin (8,9). Recently, the tsetse thrombin inhibitor (TTI), a potent (K i * ϭ 584 fM) 32-aa peptide, was purified to homogeneity from salivary gland extracts of Glossina morsitans morsitans (10). This inhibitor is highly specific for thrombin, showing no activity against a panel of 10 serine proteases, including components of the human coagulation͞thrombolytic cascade, as well as trypsin a...

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans

Cappello

Chen

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…Among the known tsetse saliva components are anti-hemostatic proteins [26], [27], [28], which include a potent anticoagulant thrombin inhibitor (TTI) [29], [30], and an anti-thrombotic apyrase (5′Nuclease) with dual inhibitory action that can bind to the fibrinogen receptor (GPIIb/IIIa) and inhibit ADP-induced platelet responses [31]. In addition, two abundant proteins (Tsal1 and Tsal2) have been described with DNA/RNA non-specific nucleic acid binding [26], [32], [33].…”

Section: Introductionmentioning

confidence: 99%

Insights into the Trypanosome-Host Interactions Revealed through Transcriptomic Analysis of Parasitized Tsetse Fly Salivary Glands

et al. 2014

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The agents of sleeping sickness disease, Trypanosoma brucei complex parasites, are transmitted to mammalian hosts through the bite of an infected tsetse. Information on tsetse-trypanosome interactions in the salivary gland (SG) tissue, and on mammalian infective metacyclic (MC) parasites present in the SG, is sparse. We performed RNA-seq analyses from uninfected and T. b. brucei infected SGs of Glossina morsitans morsitans. Comparison of the SG transcriptomes to a whole body fly transcriptome revealed that only 2.7% of the contigs are differentially expressed during SG infection, and that only 263 contigs (0.6%) are preferentially expressed in the SGs (SG-enriched). The expression of only 37 contigs (0.08%) and 27 SG-enriched contigs (10%) were suppressed in infected SG. These suppressed contigs accounted for over 55% of the SG transcriptome, and included the most abundant putative secreted proteins with anti-hemostatic functions present in saliva. In contrast, expression of putative host proteins associated with immunity, stress, cell division and tissue remodeling were enriched in infected SG suggesting that parasite infections induce host immune and stress response(s) that likely results in tissue renewal. We also performed RNA-seq analysis from mouse blood infected with the same parasite strain, and compared the transcriptome of bloodstream form (BSF) cells with that of parasites obtained from the infected SG. Over 30% of parasite transcripts are differentially regulated between the two stages, and reflect parasite adaptations to varying host nutritional and immune ecology. These differences are associated with the switch from an amino acid based metabolism in the SG to one based on glucose utilization in the blood, and with surface coat modifications that enable parasite survival in the different hosts. This study provides a foundation on the molecular aspects of the trypanosome dialogue with its tsetse and mammalian hosts, necessary for future functional investigations.

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“…However, molecular information on the individual tsetse salivary proteins and their biological activity remains scanty. Previous studies on Glossina morsitans saliva have reported the presence of a 11.3 kDa inhibitor of thrombin serine protease and esterase activities (Parker and Mant, 1979) and a 430 kDa protein fraction that inhibited the ADP-induced thrombocyte aggregation (Mant and Parker, 1981). In addition, a potent 32 AA blood meal-induced tsetse thrombin inhibitor (TTI), was characterised in salivary gland extracts.…”

Section: Introductionmentioning

confidence: 99%

The Glossina morsitans tsetse fly saliva: General characteristics and identification of novel salivary proteins

Abbeele

Caljon

Dierick³

et al. 2007

Insect Biochemistry and Molecular Biology

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Effects of Tsetse (Glossina morsitans morsitans Westw.) (Diptera: Glossinidae) Salivary Gland Homogenate on Coagulation and Fibrinolysis

Cited by 30 publications

References 11 publications

Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans

Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans

Insights into the Trypanosome-Host Interactions Revealed through Transcriptomic Analysis of Parasitized Tsetse Fly Salivary Glands

The Glossina morsitans tsetse fly saliva: General characteristics and identification of novel salivary proteins

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