Blood Clotting and Related Processes

Astrup, Tage

doi:10.1002/9780470122556.ch1

Cited by 10 publications

(4 citation statements)

References 295 publications

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“…To complete feeding ticks must keep host blood in a fluid state at the tick-feeding site and in the midgut. Thus, given that calcium (Ca 2+ ) is the fourth co-factor of the blood clotting activation pathway [ 158 ], it is conceivable that ticks may secrete Ca 2+ binding proteins into the tick-feeding site to bind and deplete Ca 2+ and prevent activation of blood clotting. Apart from potential Ca 2+ function, the four A. americanum tick saliva putative Ca 2+ binding proteins in Table 5 could perform multiple other yet unknown functions in tick physiology.…”

Section: Resultsmentioning

confidence: 99%

A 24-48 h fed Amblyomma americanum tick saliva immuno-proteome

et al. 2014

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BackgroundMultiple tick saliva proteins, the majority of which are unknown, confer tick resistance in repeatedly infested animals. The objective of this study was to identify the 24-48 h fed Amblyomma americanum tick saliva immuno-proteome. The 24-48 h tick-feeding phase is critical to tick parasitism as it precedes important events in tick biology, blood meal feeding and disease agent transmission. Fed male, 24 and 96 h fed female phage display cDNA expression libraries were biopanned using rabbit antibodies to 24 and 48 h fed A. americanum female tick saliva proteins. Biopanned immuno-cDNA libraries were subjected to next generation sequencing, de novo assembly, and bioinformatic analysis.ResultsMore than 800 transcripts that code for 24-48 h fed A. americanum immuno-proteins are described. Of the 895 immuno-proteins, 52% (464/895) were provisionally identified based on matches in GenBank. Of these, ~19% (86/464) show high level of identity to other tick hypothetical proteins, and the rest include putative proteases (serine, cysteine, leukotriene A-4 hydrolase, carboxypeptidases, and metalloproteases), protease inhibitors (serine and cysteine protease inhibitors, tick carboxypeptidase inhibitor), and transporters and/or ligand binding proteins (histamine binding/lipocalin, fatty acid binding, calreticulin, hemelipoprotein, IgG binding protein, ferritin, insulin-like growth factor binding proteins, and evasin). Others include enzymes (glutathione transferase, cytochrome oxidase, protein disulfide isomerase), ribosomal proteins, and those of miscellaneous functions (histamine release factor, selenoproteins, tetraspanin, defensin, heat shock proteins).ConclusionsData here demonstrate that A. americanum secretes a complex cocktail of immunogenic tick saliva proteins during the first 24-48 h of feeding. Of significance, previously validated immunogenic tick saliva proteins including AV422 protein, calreticulin, histamine release factor, histamine binding/lipocalins, selenoproteins, and paramyosin were identified in this screen, supporting the specificity of the approach in this study. While descriptive, this study opens opportunities for in-depth tick feeding physiology studies.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-518) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

A 24-48 h fed Amblyomma americanum tick saliva immuno-proteome

et al. 2014

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“…Multifunctional calcium binding proteins, such as calponin and calreticulin (CRT), are present in the saliva of A. variegatum but apart from depleting Ca 2+ to prevent activation of blood clotting (Astrup, 2009 ), their function is not yet known. Nevertheless, an interesting hypothesis has emerged from A. americanum CRT, which could skew a Th-2 host response to tick feeding (Kim et al, 2015 ), and which is consistent with our observation of a M2-induced profile of macrophage cytokines/metabolism by A. variegatum saliva.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

Rodrigues

Fernandez

Vercoutere

et al. 2018

Front. Cell. Infect. Microbiol.

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The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva-induced immune modulation of the host. We propose a model for the interaction between A. variegatum saliva and host immune cells that could have an effect during tick feeding by favoring pathogen dissemination or activation by reducing the efficiency of host immune response to the corresponding tick-borne diseases.

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“…The proteolytic activity of plasmin is inactivated by alpha-2-antiplasmin or alpha-2-macroglobulin, that of tPA or uPA essentially by two specific inhibitors, plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2) [4]. These observations are not new; Astrup described plasminogen activator activity, fibrinolysin, in 1950, which at that time was a term for any of various proteolytic enzymes, especially plasmin, capable of digesting fibrin in the bloodstream [5,6]. It was only a few years earlier, in 1948, that MacFarlane and Biggs had reviewed previous work on the proteolytic factors of serum since different terms had been applied to identical substances, which had led to confusion [7].…”

Section: The Early Days In Fibrinolysis Researchmentioning

confidence: 99%