Platelets: killers of parasites or patients?

Morrell, Craig N.

doi:10.1182/blood-2017-01-764621

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…Thrombocytopenia is common in severe malarial syndromes (143). Platelets respond in complex and controversial ways to malarial infection (150,151), and they are suggested to contribute to the pathophysiology of MA-ARDS (146) ( Figure 5). Nevertheless, knowledge in this area is superficial and needs to be expanded.…”

Section: Translational Reviewmentioning

confidence: 99%

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Middleton

Rondina

Schwertz

et al. 2018

Am J Respir Cell Mol Biol

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Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.

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Section: Translational Reviewmentioning

confidence: 99%

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Middleton

Rondina

Schwertz

et al. 2018

Am J Respir Cell Mol Biol

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“…A mechanism for the direct killing of Plasmodium involves platelet factor-4 (PF4), an abundant antimicrobial protein secreted by platelets, that, upon entering the cell via the Duffy-antigen – a chemokine receptor expressed by RBC30 – kills P. falciparum parasites by selectively lyzing the parasite digestive vacuole 29. However, a recent study did not reproduce the parasite killing effect of platelets in P. chabaudi -infected mice or P. falciparum -iRBC32, showing the difficulties in using in vitro and in vivo disease models to study these phenomena33, and highlighting the need for additional research in people with malaria 34…”

Section: Introductionmentioning

confidence: 99%

Platelets kill circulating parasites of all major Plasmodium species in human malaria

Kho

Barber

Johar

et al. 2018

Blood

106

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Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with ,, , or Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the species studied, particularly mature stages, and was greatest in patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4TUNEL parasites). These PF4TUNEL parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet-erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in culture. Collectively, our results indicate that platelets directly contribute to innate control of infection in human malaria.

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“…The thrombocytopenia observed during T.b.r infection could be attributed to damage to platelets by ROS [ 52 – 53 ]. Low platelet counts could also be attributable to the pooling of blood in the spleen, removal of platelets by the mononuclear phagocytic system and increased ‘consumption’ of platelets by disseminated intravascular coagulation reaction during trypanosomiasis infections [ 54 – 55 ].…”

Section: Discussionmentioning

confidence: 99%

Ginkgo biloba attenuated detrimental inflammatory and oxidative events due to Trypanosoma brucei rhodesiense in mice treated with melarsoprol

Wendo,

Mbaria,

Nyariki

et al. 2024

PLoS Negl Trop Dis

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Background The severe late stage Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei rhodesiense (T.b.r) is characterized by damage to the blood brain barrier, severe brain inflammation, oxidative stress and organ damage. Melarsoprol (MelB) is currently the only treatment available for this disease. MelB use is limited by its lethal neurotoxicity due to post-treatment reactive encephalopathy. This study sought to assess the potential of Ginkgo biloba (GB), a potent anti-inflammatory and antioxidant, to protect the integrity of the blood brain barrier and ameliorate detrimental inflammatory and oxidative events due to T.b.r in mice treated with MelB. Methodology Group one constituted the control; group two was infected with T.b.r; group three was infected with T.b.r and treated with 2.2 mg/kg melarsoprol for 10 days; group four was infected with T.b.r and administered with GB 80 mg/kg for 30 days; group five was given GB 80mg/kg for two weeks before infection with T.b.r, and continued thereafter and group six was infected with T.b.r, administered with GB and treated with MelB. Results Co-administration of MelB and GB improved the survival rate of infected mice. When administered separately, MelB and GB protected the integrity of the blood brain barrier and improved neurological function in infected mice. Furthermore, the administration of MelB and GB prevented T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia, as well as T.b.r-driven downregulation of total WBCs. Glutathione analysis showed that co-administration of MelB and GB prevented T.b.r-induced oxidative stress in the brain, spleen, heart and lungs. Notably, GB averted peroxidation and oxidant damage by ameliorating T.b.r and MelB-driven elevation of malondialdehyde (MDA) in the brain, kidney and liver. In fact, the co-administered group for the liver, registered the lowest MDA levels for infected mice. T.b.r-driven elevation of serum TNF-α, IFN-γ, uric acid and urea was abrogated by MelB and GB. Co-administration of MelB and GB was most effective in stabilizing TNFα levels. GB attenuated T.b.r and MelB-driven up-regulation of nitrite. Conclusion Utilization of GB as an adjuvant therapy may ameliorate detrimental effects caused by T.b.r infection and MelB toxicity during late stage HAT.

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Platelets: killers of parasites or patients?

Cited by 7 publications

References 14 publications

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Platelets kill circulating parasites of all major Plasmodium species in human malaria

Ginkgo biloba attenuated detrimental inflammatory and oxidative events due to Trypanosoma brucei rhodesiense in mice treated with melarsoprol

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