Involvement of Platelets in Experimental Mouse Trypanosomiasis: Evidence of Mouse Platelet Cytotoxicity against Trypanosoma equiperdum

Momi, Stefania; Perito, Stefano; Mezzasoma, Anna Maria; Bistoni, Francesco; Gresele, Paolo

doi:10.1006/expr.2000.4517

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Platelets are innately defensive also against microbial infections through the production of anti‐microbial peptides (21) and against protozoa (22,23), the latter possibly as a result of the production of thromboxane (23). It will be of interest to determine if the anti‐schistosome activity involves one or both of these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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

Stanley

Ngaiza²,

Wambayi

et al. 2003

Parasite Immunology

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The interaction between Schistosoma mansoni and platelets of non-immune mice has been studied in vivo and in vitro. A moderate thrombocytopaenia was observed in mice 2 days after they had been infected percutaneously with 200 cercariae. A rabbit anti-mouse platelet antiserum, 25 microL of which injected subcutaneously induced a nearly 900% reduction in blood platelet count 24 h later, was used to investigate the effects of severe thrombocytopaenia on S. mansoni infections. In replicate experiments worm burdens were significantly increased in mice that were thrombocytopaenic at the time of infection when compared with untreated mice. Induction of thrombocytopaenia on day 4 after infection had no effect on worm count. Platelets isolated from non-immune mice were shown to adhere to the surfaces of and kill mechanically transformed schistosomula in vitro. Platelets may thus be an innate mechanism of defence against schistosome infection, and the thrombocytopaenia that occurs during patent schistosome infections may be a strategy that helps secondarily incoming parasites evade this type of host defensiveness.

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Section: Discussionmentioning

confidence: 99%

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

Stanley

Ngaiza²,

Wambayi

et al. 2003

Parasite Immunology

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“…Preventing host response to parasite-derived TXA 2 augmented death and parasitaemia (Ashton et al, 2007). Platelets exert a direct anti-trypanosomal activity (Momi et al, 2000), and over the course of disease, there is a generalized thrombocytopenia characterized by increased platelet adherence and aggregation that likely limits the anti-parasitic action of these cells (Tanowitz et al, 1990). TXA 2 may regulate vasospasm, thrombosis, vascular permeability and endothelial cell dysfunction during acute disease; however, TXA 2 also displays immunosuppressive properties with the wild-type mice displaying minimal pathology, but TXA 2 receptor null mice exhibiting pronounced inflammation in the myocardium with an almost threefold increased in parasite load in cardiac tissue.…”

Section: 4 Endogenous Regulation Of Eicosanoids During Experimentamentioning

confidence: 99%

Bioactive Lipids in Trypanosoma cruzi Infection

Machado

Mukherjee

Weiss

et al. 2011

Advances in Parasitology

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Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite. Chagas disease remains a serious health problem in large parts of Mexico and Central and South America, where it is a major cause of morbidity and mortality. This disease is being increasingly recognized in non-endemic regions due to immigration. Heart disease develops in 10–30% of infected individuals. It is increasingly clear that parasite- and host-derived bioactive lipids potently modulate disease progression. Many of the changes that occur during acute and chronic Chagas disease can be accounted for by the effects of arachidonic acid (AA)-derived lipids such as leukotrienes, lipoxins, H(P)ETEs, prostaglandins (PGs) and thromboxane. During the course of infection with T. cruzi, changes in circulating levels of AA metabolites are observed. Antagonism of PG synthesis with cyclooxygenase (COX) inhibitors has both beneficial and adverse effects. Treatment with COX inhibitors during acute infection may result in increased parasite load and mortality. However, treatment instituted during chronic infection may be beneficial with no increase in mortality and substantial improvement with cardiac function. Recently, T. cruzi infection of mice deficient in AA biosynthetic enzymes for various pathways has yielded more insightful data than pharmacological inhibition and has highlighted the potential deleterious effects of inhibitors due to “off-target” actions. Using COX-1 null mice, it was observed that parasite biosynthesis is dependent upon host metabolism, that the majority of TXA2 liberated during T. cruzi infection is derived from the parasite and that this molecule may act as a quorum sensor to control parasite growth/differentiation. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to, and maintenance of, the chronic stage of the disease. It is also likely that the same mediators that initially function to ensure host survival may later contribute to cardiovascular damage. Collectively, the eicosanoids represent a new series of targets for therapy in Chagas disease with defined potential therapeutic windows in which to apply these agents for greatest effect. A deeper understanding of the mechanism of action of non-steroidal anti-inflammatory drugs may provide clues to the differences between host responses in acute and chronic T. cruzi infection.

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“…However, it is apparent that only a few platelets express both FceRI and FceRII simultaneously (Joseph et al, 1997), and these may represent a subset of platelets that react in a dichotic manner to inflammatory stimuli compared to 'normal' platelets. The involvement of platelets in allergic inflammation may well represent inappropriate actions of platelets commonly displayed in IgE-mediated immunity against helminth and protozoan parasitic infections (Joseph et al, 1983(Joseph et al, , 1985Momi et al, 2000). Platelet activation via FceRI has been shown to induce the release of 5-HT, ROS and RANTES, demonstrating that platelets may play an important role in the progression of allergic inflammation via IgE-dependent mechanisms (Joseph et al, 1986;Klouche et al, 1997).…”

Section: Platelet Involvement In Antigen Recognitionmentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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Involvement of Platelets in Experimental Mouse Trypanosomiasis: Evidence of Mouse Platelet Cytotoxicity against Trypanosoma equiperdum

Cited by 5 publications

References 31 publications

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

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

Bioactive Lipids in Trypanosoma cruzi Infection

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

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