Platelet Secretory Activities in Acute Malaria &lt;i&gt;(Plasmodium falciparum)&lt;/i&gt; Infection

Essien, E M; Ebhota, M I

doi:10.1159/000206720

Cited by 42 publications

(27 citation statements)

References 8 publications

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“…Platelet accumulation in cerebral microvessels of patients who die from CM reveal a possible role of platelets and CXCL4 in the pathogenesis of CM [34]. Elevated levels of CXCL4 have been associated with acute human malaria [22] and in ECM [68]. CXCL4 stimulates macrophage and TNF-α, a key proinflammatory molecule associated with the development of CM [31,52,78].…”

Section: Discussionmentioning

confidence: 99%

“…Among the ligands of CXCR3, CXCL4 is described to be the most powerful angiostatic chemokine [3,63]. Significantly elevated plasma levels of this chemokine have been observed in acute P. falciparum infection in human [22,60] and found to mediate murine Experimental Cerebral Malaria (ECM) pathogenesis by promoting a pro-inflammatory environment involving increased T cell CXCR3 expression and monocyte activation [68,69].…”

Section: Introductionmentioning

confidence: 99%

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CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

et al. 2011

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Abstract. Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience shortand long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p < 0.0001) and CMS (p < 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

et al. 2011

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“…51 Taken together, these studies and others provide experimental and clinical evidence that platelets are key immune effector cells in malaria. 52,53 Dengue, a mosquito-borne viral infection, has variable clinical manifestations. Nevertheless, especially in more severe cases, marked thrombocytopenia, hemorrhage, "capillary leak," and shock may occur.…”

Section: Clinical Implications Of Altered Platelet Functions In Sepsismentioning

confidence: 99%

Platelets in infectious disease

Middleton

Rondina

2016

Hematology

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Sepsis is a dynamic, acute, infectious disease syndrome characterized by dysregulated thrombo-inflammatory responses. The high mortality associated with sepsis has been recognized since the earliest clinicians' writings. Despite this, advances in the treatment of sepsis have been more modest. This is limited, in part, by the heterogeneity in the definition, population, presentation, and causal factors of infectious syndromes. Given the persistently high morbidity and mortality associated with sepsis, a better understanding of the dysregulated cellular biology underpinning sepsis is needed. Platelets are small, anucleate cells that have hemostatic, inflammatory, and immune-mediating properties. Platelets are the second most common circulating blood cell, and emerging evidence suggests that platelets serve as sentinel and effector cells during infectious syndromes. Nevertheless, the molecular and functional changes that occur in platelets during sepsis, and their impact on the clinical course of infected patients, remain incompletely understood. In this review, we first highlight the complex and dynamic pathophysiology characteristics of acute, systemic infections and we then discuss established and emerging evidence of the roles of platelets in sepsis. Learning Objectives• Understand the systemic pathophysiology and thromboinflammation characteristic of human infectious disease syndromes • Review the role of platelets in sepsis as modulating host hemostatic, inflammatory, and immune activities

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“…1 Clinical studies of patients with P falciparum indicate a marked procoagulant state with consumption of clotting factors, the presence of fibrin dimers, and decreased levels of the anticoagulants protein C and S [2][3][4] ; the procoagulant state correlates with the development of severe malaria. Grau and colleagues 5 have proposed that platelet activation and adherence contributes to the development of severe malaria.…”

Section: Introductionmentioning

confidence: 99%

Platelet depletion by anti-CD41 (αIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines

Heyde

Gramaglia

Sun

et al. 2005

Blood

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Accumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (ESM) elicited by infection with Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited significantly (P < .001) increased survival from ESM compared with infection controls, indicating that platelets function early in the disease. In contrast, groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited similar mortality as controls.Because platelet depletion by anti-CD41 mAb on day 4 of infection did not protect mice, and platelet adherence occurs on day 6, platelet adherence to endothelium is not required to mediate malarial pathogenesis. Few platelet microparticles were detected in the blood during the course of malaria, but large numbers of erythrocyte vesicles, microparticles, and debris were detected. The protective effect of early anti-CD41 mAb treatment was independent of the number of platelets, platelet microparticles, erythrocyte-platelet conjugates, and erythrocyte vesicles. Mice IntroductionOne of the hallmarks of cerebral malaria, which is caused by infection with Plasmodium falciparum, is petechial hemorrhaging into the brain, indicating that platelets may play a crucial role in malarial pathogenesis. 1 Clinical studies of patients with P falciparum indicate a marked procoagulant state with consumption of clotting factors, the presence of fibrin dimers, and decreased levels of the anticoagulants protein C and S 2-4 ; the procoagulant state correlates with the development of severe malaria. Grau and colleagues 5 have proposed that platelet activation and adherence contributes to the development of severe malaria. Patients with severe falciparum malaria exhibit profound thrombocytopenia, and platelet accumulation in the brains of children who have succumbed to severe falciparum malaria is significantly higher than platelet accumulation in the brains of patients who died from other coma complications. [6][7][8][9] These clinical results in humans with malaria provide the impetus for parallel mechanistic studies in animal models. Extrapolation of results from mouse models of severe malaria must be cautious because the P falciparum species of the malarial parasite cannot be used in rodent models of severe malaria because they do not replicate in mouse erythrocytes, and there are also differences between rodents and humans. Nevertheless, direct evidence for the importance of platelets in malarial pathogenesis has come from the P berghei model of severe malaria. 10,11 CD41/CD61 (␣IIb/␤3 integrin heterodimer, also known as gpIIb/IIIa) is an important molecule in platelet biology and its major function is contributing to expansion of clot formation and platelet adhesion to the microvasculature. 12-14 Our previous studies indicate that platelet adhesion during experimental severe malaria (ESM) occurs primarily in venules within the pial microvasculature and that CD41 plays an imp...

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Platelet Secretory Activities in Acute Malaria <i>(Plasmodium falciparum)</i> Infection

Cited by 42 publications

References 8 publications

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

Platelets in infectious disease

Platelet depletion by anti-CD41 (αIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines

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