Platelets as an innate defence mechanism against <i>Schistosoma mansoni</i> infections in mice

Stanley, Ronald G.; Ngaiza, Justinian R.; Wambayi, E.; Lewis, Jennifer A.; Doenhoff, Michael J.

doi:10.1111/j.1365-3024.2003.00656.x

Cited by 24 publications

(22 citation statements)

References 21 publications

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“…This is particularly relevant to the metazoan parasite S. mansoni as it enters the bloodstream. Experimental percutaneous infection of mice with S. mansoni results in a transient thrombocytopenia 2 days after infection, at about the stage that the organism reaches the bloodstream, suggesting that platelet activation and attachment of platelets to larvae is a host defense mechanism against infection (139). This is supported by the observation that platelets can attach to larvae in vitro.…”

Section: Interference With P2 Receptor Signaling By Parasitessupporting

confidence: 69%

“…This is supported by the observation that platelets can attach to larvae in vitro. However, a few days after infection, platelet levels are similar in infected and control animals, suggesting that the larvae become resistant to platelet defense mechanisms (139). Since the larval forms of S. mansoni express both SmATPDase 1 and SmATPDase 2 (45,96), it is possible that upon entry of the parasite into the bloodstream, exposure to platelets leads to increased expression of the enzymes.…”

Section: Interference With P2 Receptor Signaling By Parasitesmentioning

confidence: 99%

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Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Sansom

Robson

Hartland

2008

Microbiol Mol Biol Rev

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SUMMARYIn humans, purinergic signaling plays an important role in the modulation of immune responses through specific receptors that recognize nucleoside tri- and diphosphates as signaling molecules. Ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTPDases) have important roles in the regulation of purinergic signaling by controlling levels of extracellular nucleotides. This process is key to pathophysiological protective responses such as hemostasis and inflammation. Ecto-NTPDases are found in all higher eukaryotes, and recently it has become apparent that a number of important parasitic pathogens of humans express surface-located NTPDases that have been linked to virulence. For those parasites that are purine auxotrophs, these enzymes may play an important role in purine scavenging, although they may also influence the host response to infection. Although ecto-NTPDases are rare in bacteria, expression of a secreted NTPDase in Legionella pneumophila was recently described. This ecto-enzyme enhances intracellular growth of the bacterium and potentially affects virulence. This discovery represents an important advance in the understanding of the contribution of other microbial NTPDases to host-pathogen interactions. Here we review other progress made to date in the characterization of ecto-NTPDases from microbial pathogens, how they differ from mammalian enzymes, and their association with organism viability and virulence. In addition, we postulate how ecto-NTPDases may contribute to the host-pathogen interaction by reviewing the effect of selected microbial pathogens on purinergic signaling. Finally, we raise the possibility of targeting ecto-NTPDases in the development of novel anti-infective agents based on potential structural and clear enzymatic differences from the mammalian ecto-NTPDases.

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Section: Interference With P2 Receptor Signaling By Parasitessupporting

confidence: 69%

Section: Interference With P2 Receptor Signaling By Parasitesmentioning

confidence: 99%

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Sansom

Robson

Hartland

2008

Microbiol Mol Biol Rev

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“…45,46 This binding was shown to be responsible for the associated thrombocytopenia with particular involvement of platelet GP␣ IIb ␤ 3 . 45 Internalization of bacteria and viruses has been seen in megakaryocytes and platelets 47 and adenoviral particles have recently been documented inside platelets within 5 minutes of intravenous viral administration.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance

Othman¹,

Labelle²,

Mazzetti³

et al. 2006

Blood

194

202

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Thrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectincoated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyteendothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration. IntroductionAcute thrombocytopenia has been consistently reported following intravenous administration of adenovirus. [1][2][3] Thrombocytopenia is transient and vector dose-dependent but the mechanism underlying this adverse event currently remains unclear.P-selectin is a member of the selectin family of cell adhesion molecules that mediate binding to specific carbohydrate-containing ligands. The protein is localized in the ␣ granules of platelets and the Weibel-Palade bodies of endothelial cells. 4,5 The most clearly identified ligand for P-selectin is PSGL-1, which is detected on the majority of leukocytes and also present in small amounts on platelets. 6,7 P-selectin supports initial tethering of leukocytes to activated endothelial cells and to activated platelets and mediates leukocyte rolling on the endothelial cell surface. 8 A soluble form of P-selectin resulting from proteolytic shedding of the extracellular domain has been detected in human 9 and mouse 10 plasma and was found to maintain the requirements for ligand binding. 11 Elevated levels of plasma P-selectin are seen in a variety of inflammatory, autoimmune, and thrombotic disorders. 12,13 A critical step in the response to vascular injury is the interaction between platelets and the adhesive protein von Willebrand factor (VWF), which mediates platelet translocation and adhesion to the exposed subendothelium. 14 VWF binding to platelets is mediated through platelet GPIb and this interaction acts as a complementary binding event to the tethering of leukocytes to platelets through a Mac1-P-selectin interaction. 15 Furthermore, activation of the endothelium is...

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“…The relevance of the interaction between Schis tosoma mansoni and platelets has been studied in vivo and in vitro [193]. Isolated platelets effi ciently adhere and kill schistosomula (the migra tory larval form) in vitro [193,194].…”

Section: Worm Infectionsmentioning

confidence: 99%

Platelets as Immune Cells in Infectious Diseases

et al. 2013

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Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation. Consequently, platelets exert antimicrobial effector mechanisms, but also initiate an intense crosstalk with other arms of the innate and adaptive immunity, including neutrophils, monocytes/macrophages, dendritic cells, B cells and T cells. There is a fragile balance between beneficial antimicrobial effects and detrimental reactions that contribute to the pathogenesis, and many pathogens have developed mechanisms to influence these two outcomes. This review aims to highlight aspects of the interaction strategies between platelets and pathogenic bacteria, viruses, fungi and parasites, in addition to the subsequent networking between platelets and other immune cells, and the relevance of these processes for the pathogenesis of infections.

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Platelets as an innate defence mechanism against Schistosoma mansoni infections in mice

Cited by 24 publications

References 21 publications

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance

Platelets as Immune Cells in Infectious Diseases

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