Platelet-endothelial cell interactions in cerebral malaria: The end of a cordial understanding

Dorothée Faille; Fatima El-Assaad; Marie-Christine Alessi; Thierry Fusai; Valéry Combes; Georges E. Grau

doi:10.1160/TH09-05-0337

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(06): 1093-1102
DOI: 10.1160/TH09-05-0337

Theme Issue Article

Schattauer GmbH

Platelet-endothelial cell interactions in cerebral malaria: The end of a cordial understanding

Dorothée Faille

¹Department of Pathology, University of Sydney, Camperdown, New South Wales, Australia

²Unitéde Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santédes Armées, Marseille, France

³Inserm U626, Aix-Marseille Université, Facultéde Médecine, Marseille, France

,

Fatima El-Assaad

¹Department of Pathology, University of Sydney, Camperdown, New South Wales, Australia

,

Marie-Christine Alessi

³Inserm U626, Aix-Marseille Université, Facultéde Médecine, Marseille, France

,

Thierry Fusai

²Unitéde Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santédes Armées, Marseille, France

,

Valéry Combes

¹Department of Pathology, University of Sydney, Camperdown, New South Wales, Australia

,

Georges E. Grau

¹Department of Pathology, University of Sydney, Camperdown, New South Wales, Australia

› Author Affiliations

Abstract

Summary

Cerebral malaria is an acute encephalopathy evolving from an infection with Plasmodium falciparum which kills more than one million people each year. Brain tissues from patients who died with cerebral malaria revealed multifocal capillary obstruction by parasitised red blood cells, platelets, and leukocytes. Many studies are unified in their proposal of two major hypotheses consisting of cell adhesion to the brain endothelium and excessive immune stimulation resulting in further vascular inflammation, prothrombotic cell activation, mechanical obstruction of cerebral capillaries and, consequently, blood-brain barrier disruption. Platelets and endothelial cells communicate on multiple levels. Infection-induced changes in platelets and endothelial cells occur in cerebral malaria, resulting in their concomitant activation, increased interactions between these two cell types, and a secondary procoagulant or hypercoagulable state. Here we review evidence for these mechanisms and highlight the possible role of platelets as effectors of endothelial damage in cerebral malaria. A better understanding of the complex regulation of these various interactions between brain endothelial cells and platelets in the context of cerebral malaria may prove useful in the development of new approaches to the treatment of this disease.

Keywords

Endothelial cells - platelet immunology - infectious diseases - microparticles

Full Text

References

References
1 WHO. World Malaria Report 2008. Available at www.who.int/malaria/wmr2008/malaria2008.pdf Accessed June 22, 2009
2 Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000; 94 (Suppl. 01) S1-90.
3 Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther 1998; 79: 1-53.
4 Brewster DR, Kwiatkowski D, White NJ. Neurological sequelae of cerebral malaria in children. Lancet 1990; 336: 1039-1043.
5 Silamut K, Phu NH, Whitty C. et al. A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. Am J Pathol 1999; 155: 395-410.
6 Riganti M, Pongponratn E, Tegoshi T. et al. Human cerebral malaria in Thailand: a clinico-pathological correlation. Immunol Lett 1990; 25: 199-205.
7 Berendt AR, Tumer GD, Newbold CI. Cerebral malaria: the sequestration hypothesis. Parasitol Today 1994; 10: 412-414.
8 Idro R, Jenkins NE, Newton CR. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 2005; 04: 827-840.
9 Pongponratn E, Riganti M, Punpoowong B. et al. Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study. Am J Trop Med Hyg 1991; 44: 168-175.
10 Medana IM, Mai NT, Day NP. et al. Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathol Appl Neurobiol 2001; 27: 421-433.
11 Clark IA, Rockett KA. The cytokine theory of human cerebral malaria. Parasitol Today 1994; 10: 410-412.
12 Grau GE, de Kossodo S. Cerebral malaria: mediators, mechanical obstruction or more?. Parasitol Today 1994; 10: 408-409.
13 van der Heyde HC, Nolan J, Combes V. et al. A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 2006; 22: 503-508.
14 Francischetti IM, Seydel KB, Monteiro RQ. Blood coagulation, inflammation, and malaria. Microcirculation 2008; 15: 81-107.
15 Francischetti IM. Does activation of the blood coagulation cascade have a role in malaria pathogenesis?. Trends Parasitol 2008; 24: 258-263.
16 Gerardin P, Rogier C, Ka AS. et al. Prognostic value of thrombocytopenia in African children with falciparum malaria. Am J Trop Med Hyg 2002; 66: 686-691.
17 Mohanty D, Ghosh K, Nandwani SK. et al. Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria. Am J Hematol 1997; 54: 23-29.
18 Holst FG, Hemmer CJ, Foth C. et al. Low levels of fibrin-stabilizing factor (factor XIII) in human Plasmodium falciparum malaria: correlation with clinical severity. Am J Trop Med Hyg 1999; 60: 99-104.
19 Borochovitz D, Crosley AL, Metz J. Disseminated intravascular coagulation with fatal haemorrhage in cerebral malaria. Br Med J 1970; 02: 710.
20 Turner G. Cerebral malaria. Brain Pathol 1997; 07: 569-582.
21 Kelton JG, Keystone J, Moore J. et al. Immune-mediated thrombocytopenia of malaria. J Clin Invest 1983; 71: 832-836.
22 Mohanty D, Marwaha N, Ghosh K. et al. Functional and ultrastructural changes of platelets in malarial infection. Trans R Soc Trop Med Hyg 1988; 82: 369-375.
23 Hollestelle MJ, Donkor C, Mantey EA. et al. von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation. Br J Haematol 2006; 133: 562-569.
24 McMorran BJ, Marshall VM, de Graaf C. et al. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science 2009; 323: 797-800.
25 Newbold C, Warn P, Black G. et al. Receptor-specific adhesion and clinical disease in Plasmodium falciparum . Am J Trop Med Hyg 1997; 57: 389-398.
26 Grau GE, Tacchini-Cottier F, Vesin C. et al. TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction. Eur Cytokine Netw 1993; 04: 415-419.
27 Grau GE, Mackenzie CD, Carr RA. et al. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 2003; 187: 461-466.
28 Mannel DN, Grau GE. Role of platelet adhesion in homeostasis and immunopathology. Mol Pathol 1997; 50: 175-185.
29 Pongponratn E, Riganti M, Harinasuta T. et al. Electron microscopy of the human brain in cerebral malaria. Southeast Asian J Trop Med Public Health 1985; 16: 219-227.
30 Ho M, White NJ. Molecular mechanisms of cytoadherence in malaria. Am J Physiol 1999; 276: C1231-1242.
31 Treutiger CJ, Heddini A, Fernandez V. et al. PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat Med 1997; 03: 1405-1408.
32 Fried M, Duffy PE. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 1996; 272: 1502-1504.
33 Aird WC. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 2007; 100: 174-190.
34 Kaul DK, Nagel RL, Llena JF. et al. Cerebral malaria in mice: demonstration of cytoadherence of infected red blood cells and microrheologic correlates. Am J Trop Med Hyg 1994; 50: 512-521.
35 Frenette PS, Johnson RC, Hynes RO. et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A 1995; 92: 7450-7454.
36 Russell J, Cooper D, Tailor A. et al. Low venular shear rates promote leukocyte-dependent recruitment of adherent platelets. Am J Physiol Gastrointest Liver Physiol 2003; 284: G123-129.
37 Turner GD, Morrison H, Jones M. et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 1994; 145: 1057-1069.
38 Favre N, Da Laperousaz C, Ryffel B. et al. Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect 1999; 01: 961-968.
39 Fry AE, Auburn S, Diakite M. et al. Variation in the ICAM1 gene is not associated with severe malaria phenotypes. Genes Immun 2008; 09: 462-469.
40 Combes V, Rosenkranz AR, Redard M. et al. Pathogenic role of P-selectin in experimental cerebral malaria: importance of the endothelial compartment. Am J Pathol 2004; 164: 781-786.
41 Li J, Chang WL, Sun G. et al. Intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain. J Investig Med 2003; 51: 128-140.
42 Chang WL, Li J, Sun G. et al. P-selectin contributes to severe experimental malaria but is not required for leukocyte adhesion to brain microvasculature. Infect Immun 2003; 71: 1911-1918.
43 Sun G, Chang WL, Li J. et al. Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria. Infect Immun 2003; 71: 6553-6561.
44 Piguet PF, Vesin C, Donati Y. et al. Urokinase receptor (uPAR, CD87) is a platelet receptor important for kinetics and TNF-induced endothelial adhesion in mice. Circulation 1999; 99: 3315-3321.
45 Piguet PF, Da Laperrousaz C, Vesin C. et al. Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice. Infect Immun 2000; 68: 3822-3829.
46 van der Heyde HC, Gramaglia I, Sun G. et al. Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines. Blood 2005; 105: 1956-1963.
47 Srivastava K, Cockburn IA, Swaim A. et al. Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell Host Microbe 2008; 04: 179-187.
48 Theilmeier G, Michiels C, Spaepen E. et al. Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia. Blood 2002; 99: 4486-4493.
49 Lou J, Donati YR, Juillard P. et al. Platelets play an important role in TNF-induced microvascular endothelial cell pathology. Am J Pathol 1997; 151: 1397-1405.
50 Udomsangpetch R, Taylor BJ, Looareesuwan S. et al. Receptor specificity of clinical Plasmodium falciparum isolates: nonadherence to cell-bound E-selectin and vascular cell adhesion molecule-1. Blood 1996; 88: 2754-2760.
51 Greenwalt DE, Scheck SH, Rhinehart-Jones T. Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet. J Clin Invest 1995; 96: 1382-1388.
52 Pain A, Ferguson DJ, Kai O. et al. Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. Proc Natl Acad Sci U S A 2001; 98: 1805-1810.
53 Biswas AK, Hafiz A, Banerjee B. et al. Plasmodium falciparum uses gC1qR/HABP1/p32 as a receptor to bind to vascular endothelium and for platelet-mediated clumping. PLoS Pathog 2007; 03: 1271-1280.
54 Wassmer SC, Lepolard C, Traore B. et al. Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis 2004; 189: 180-189.
55 Burnier L, Fontana P, Kwak BR. et al. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost 2009; 101: 439-451.
56 Piguet PF, Kan CD, Vesin C. Thrombocytopenia in an animal model of malaria is associated with an increased caspase-mediated death of thrombocytes. Apoptosis 2002; 07: 91-98.
57 Nomura S, Inami N, Iwasaka T. Differences in functional roles between activated platelets and platelet-derived microparticles. Thromb Haemost 2007; 98: 1143-1144.
58 Combes V, Coltel N, Faille D. et al. Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int J Parasitol 2006; 36: 541-546.
59 Barry OP, Pratico D, Savani RC. et al. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998; 102: 136-144.
60 Barry OP, Pratico D, Lawson JA. et al. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest 1997; 99: 2118-2127.
61 Janowska-Wieczorek A, Majka M, Kijowski J. et al. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 2001; 98: 3143-3149.
62 Salanova B, Choi M, Rolle S. et al. Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils. J Biol Chem 2007; 282: 27960-27969.
63 Faille D, Combes V, Mitchell AJ. et al. Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. Faseb J. 2009 prepublished online, doi:10.1096/fj. 09-135822.
64 Hviid L, Theander TG, Elhassan IM. et al. Increased plasma levels of soluble ICAM-1 and ELAM-1 (E-selectin) during acute Plasmodium falciparum malaria. Immunol Lett 1993; 36: 51-58.
65 Boehme MW, Werle E, Kommerell B. et al. Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. Clin Investig 1994; 72: 598-603.
66 Jakobsen PH, Morris-Jones S, Ronn A. et al. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. Immunology 1994; 83: 665-669.
67 Turner GD, Ly VC, Nguyen TH. et al. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 1998; 152: 1477-1487.
68 Tripathi AK, Sullivan DJ, Stins MF. Plasmodium falciparum-infected erythrocytes increase intercellular adhesion molecule 1 expression on brain endothelium through NF-kappaB. Infect Immun 2006; 74: 3262-3270.
69 Gawaz M, Neumann FJ, Dickfeld T. et al. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 1998; 98: 1164-1171.
70 Jakobsen PH, Morris-Jones S, Theander TG. et al. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria. Clin Exp Immunol 1994; 96: 98-103.
71 Hunt NH, Grau GE. Cytokines: accelerators and brakes in the pathogenesis of cerebral malaria. Trends Immunol 2003; 24: 491-499.
72 Weiser S, Miu J, Ball HJ. et al. Interferon-gamma synergises with tumour necrosis factor and lymphotoxin-alpha to enhance the mRNA and protein expression of adhesion molecules in mouse brain endothelial cells. Cytokine 2007; 37: 84-91.
73 Rudin W, Eugster HP, Bordmann G. et al. Resistance to cerebral malaria in tumor necrosis factoralpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response. Am J Pathol 1997; 150: 257-266.
74 Grau GE, Taylor TE, Molyneux ME. et al. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989; 320: 1586-1591.
75 Lou J, Gasche Y, Zheng L. et al. Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria. Eur J Immunol 1998; 28: 3989-4000.
76 Lucas R, Juillard P, Decoster E. et al. Crucial role of tumor necrosis factor (TNF) receptor 2 and membranebound TNF in experimental cerebral malaria. Eur J Immunol 1997; 27: 1719-1725.
77 von Zur Muhlen C, Sibson NR, Peter K. et al. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. J Clin Invest 2008; 118: 1198-1207.
78 de Mast Q, Groot E, Lenting PJ. et al. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis 2007; 196: 622-628.
79 de Mast Q, Groot E, Asih PB. et al. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg 2009; 80: 492-498.
80 Larkin D, de Laat B, Jenkins PV. et al. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition. PLoS Pathog 2009; 05: e1000349.
81 Wu KK, Thiagarajan P. Role of endothelium in thrombosis and hemostasis. Annu Rev Med 1996; 47: 315-331.
82 Horstmann RD, Dietrich M. Haemostatic alterations in malaria correlate to parasitaemia. Blut 1985; 51: 329-335.
83 Henn V, Slupsky JR, Grafe M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
84 Slupsky JR, Kalbas M, Willuweit A. et al. Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40. Thromb Haemost 1998; 80: 1008-1014.
85 Piguet PF, Kan CD, Vesin C. et al. Role of CD40-CVD40L in mouse severe malaria. Am J Pathol 2001; 159: 733-742.
86 von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 2007; 100: 27-40.
87 Weber C. Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 2005; 96: 612-616.
88 Essien EM, Ebhota MI. Platelet secretory activities in acute malaria (Plasmodium falciparum) infection. Acta Haematol 1983; 70: 183-188.
89 Miu J, Mitchell AJ, Muller M. et al. Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J Immunol 2008; 180: 1217-1230.
90 John CC, Opika-Opoka R, Byarugaba J. et al. Low levels of RANTES are associated with mortality in children with cerebral malaria. J Infect Dis 2006; 194: 837-845.
91 Ochiel DO, Awandare GA, Keller CC. et al. Differential regulation of beta-chemokines in children with Plasmodium falciparum malaria. Infect Immun 2005; 73: 4190-4197.
92 Were T, Hittner JB, Ouma C. et al. Suppression of RANTES in children with Plasmodium falciparum malaria. Haematologica 2006; 91: 1396-1399.
93 Terao S, Yilmaz G, Stokes KY. et al. Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion. Stroke 2008; 39: 2560-2570.
94 Belnoue E, Kayibanda M, Deschemin JC. et al. CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 2003; 101: 4253-4259.
95 Mause SF, von Hundelshausen P, Zernecke A. et al. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1512-1518.
96 Prakash D, Fesel C, Jain R. et al. Clusters of cytokines determine malaria severity in Plasmodium falciparum-infected patients from endemic areas of Central India. J Infect Dis 2006; 194: 198-207.
97 Brown H, Turner G, Rogerson S. et al. Cytokine expression in the brain in human cerebral malaria. J Infect Dis 1999; 180: 1742-1746.
98 Gawaz M, Brand K, Dickfeld T. et al. Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin- 1-dependent mechanism. Implications for atherogenesis. Atherosclerosis 2000; 148: 75-85.
99 Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 2000; 23: 618-625.
100 Rockett KA, Awburn MM, Rockett EJ. et al. Tumor necrosis factor and interleukin-1 synergy in the context of malaria pathology. Am J Trop Med Hyg 1994; 50: 735-742.
101 Omer FM, Riley EM. Transforming growth factor beta production is inversely correlated with severity of murine malaria infection. J Exp Med 1998; 188: 39-48.
102 Park SK, Yang WS, Lee SK. et al. TGF-beta(1) down-regulates inflammatory cytokine-induced VCAM-1 expression in cultured human glomerular endothelial cells. Nephrol Dial Transplant 2000; 15: 596-604.
103 Baenziger NL, Brodie GN, Majerus PW. A thrombin-sensitive protein of human platelet membranes. Proc Natl Acad Sci U S A 1971; 68: 240-243.
104 Aikawa M, Brown A, Smith CD. et al. A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys. Am J Trop Med Hyg 1992; 46: 391-397.
105 Narizhneva NV, Razorenova OV, Podrez EA. et al. Thrombospondin-1 up-regulates expression of cell adhesion molecules and promotes monocyte binding to endothelium. Faseb J 2005; 19: 1158-1160.
106 Jimenez B, Volpert OV, Crawford SE. et al. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med 2000; 06: 41-48.
107 Persidsky Y, Ramirez SH, Haorah J. et al. Bloodbrain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 2006; 01: 223-236.
108 Brown H, Hien TT, Day N. et al. Evidence of blood-brain barrier dysfunction in human cerebral malaria. Neuropathol Appl Neurobiol 1999; 25: 331-340.
109 Brown H, Rogerson S, Taylor T. et al. Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg 2001; 64: 207-213.
110 Tripathi AK, Sullivan DJ, Stins MF. Plasmodium falciparum-infected erythrocytes decrease the integrity of human blood-brain barrier endothelial cell monolayers. J Infect Dis 2007; 195: 942-950.
111 Pino P, Vouldoukis I, Dugas N. et al. Redox-dependent apoptosis in human endothelial cells after adhesion of Plasmodium falciparum-infected erythrocytes. Ann N Y Acad Sci 2003; 1010: 582-586.
112 Pino P, Vouldoukis I, Kolb JP. et al. Plasmodium falciparum--infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 2003; 187: 1283-1290.
113 Toure FS, Ouwe-Missi-Oukem-Boyer O, Bisvigou U. et al. Apoptosis: a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria. Parasite Immunol 2008; 30: 47-51.
114 Hemmer CJ, Lehr HA, Westphal K. et al. Plasmodium falciparum Malaria: reduction of endothelial cell apoptosis in vitro. Infect Immun 2005; 73: 1764-1770.
115 Wilson NO, Huang MB, Anderson W. et al. Soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial and neuroglia cells. Mol Biochem Parasitol 2008; 162: 172-176.
116 Medana IM, Lindert RB, Wurster U. et al. Cerebrospinal fluid levels of markers of brain parenchymal damage in Vietnamese adults with severe malaria. Trans R Soc Trop Med Hyg 2005; 99: 610-617.
117 Wassmer SC, Combes V, Candal FJ. et al. Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum . Infect Immun 2006; 74: 645-653.
118 Wassmer SC, de Souza JB, Frere C. et al. TGFbeta1 released from activated platelets can induce TNFstimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. J Immunol 2006; 176: 1180-1184.
119 Kuckleburg CJ, Tiwari R, Czuprynski CJ. Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and –9 and generation of reactive oxygen species. Thromb Haemost 2008; 99: 363-372.
120 Kisucka J, Chauhan AK, Zhao BQ. et al. Elevated levels of soluble P-selectin in mice alter blood brain barrier function, exacerbate stroke and promote atherosclerosis. Blood 2009; 113: 6015-6022.
121 Abid Hussein MN, Boing AN, Sturk A. et al. Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb Haemost 2007; 98: 1096-1107.
122 Abid Hussein MN, Nieuwland R, Hau CM. et al. Cell-derived microparticles contain caspase 3 in vitro and in vivo. J Thromb Haemost 2005; 03: 888-896.
123 Boing AN, Hau CM, Sturk A. et al. Platelet microparticles contain active caspase 3. Platelets 2008; 19: 96-103.
124 Gambim MH, do Carmo OAde, Marti L. et al. Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care 2007; 11: R107.
125 Preissner KT, Kanse SM, May AE. Urokinase receptor: a molecular organizer in cellular communication. Curr Opin Cell Biol 2000; 12: 621-628.
126 He CS, Wilhelm SM, Pentland AP. et al. Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci U S A 1989; 86: 2632-2636.
127 Hanemaaijer R, Koolwijk P, le Clercq L. et al. Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. Biochem J 1993; 296 Pt (03) 803-809.
128 May AE, Kalsch T, Massberg S. et al. Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 2002; 106: 2111-2117.
129 Fauser S, Deininger MH, Kremsner PG. et al. Lesion associated expression of urokinase-type plasminogen activator receptor (uPAR, CD87) in human cerebral malaria. J Neuroimmunol 2000; 111: 234-240.
130 Van den Steen PE, Van Aelst I, Starckx S. et al. Matrix metalloproteinases, tissue inhibitors of MMPs and TACE in experimental cerebral malaria. Lab Invest 2006; 86: 873-888.
131 Stellos K, Gawaz M. Platelet interaction with progenitor cells: potential implications for regenerative medicine. Thromb Haemost 2007; 98: 922-929.
132 Gyan B, Goka BQ, Adjei GO. et al. Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in african children. Am J Trop Med Hyg 2009; 80: 541-546.
133 Dernbach E, Randriamboavonjy V, Fleming I. et al. Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors. Basic Res Cardiol 2008; 103: 572-581.
134 Theiss HD, David R, Engelmann MG. et al. Circulation of CD34+progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM). Eur Heart J 2007; 28: 1258-1264.
135 Delgado MB, Clark-Lewis I, Loetscher P. et al. Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. Eur J Immunol 2001; 31: 699-707.
136 McQuibban GA, Butler GS, Gong JH. et al. Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 2001; 276: 43503-43508.
137 Zhang K, McQuibban GA, Silva C. et al. HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat Neurosci 2003; 06: 1064-1071.
138 Baj-Krzyworzeka M, Majka M, Pratico D. et al. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp Hematol 2002; 30: 450-459.
139 English D, Garcia JG, Brindley DN. Platelet-released phospholipids link haemostasis and angiogenesis. Cardiovasc Res 2001; 49: 588-599.
140 Pilorget A, Annabi B, Bouzeghrane F. et al. Inhibition of angiogenic properties of brain endothelial cells by platelet-derived sphingosine-1-phosphate. J Cereb Blood Flow Metab 2005; 25: 1171-1182.
141 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110.
142 Satoh K, Yoshida H, Imaizumi TA. et al. Production of platelet-activating factor by porcine brain microvascular endothelial cells in culture. Thromb Haemost 1995; 74: 1335-1339.
143 Prescott SM, Zimmerman GA, McIntyre TM. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci U S A 1984; 81: 3534-3538.
144 Deininger MH, Kremsner PG, Meyermann R. et al. Focal accumulation of cyclooxygenase-1 (COX-1) and COX-2 expressing cells in cerebral malaria. J Neuroimmunol 2000; 106: 198-205.
145 Ball HJ, MacDougall HG, McGregor IS. et al. Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria. J Infect Dis 2004; 189: 751-758.
146 Perkins DJ, Kremsner PG, Weinberg JB. Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria. J Infect Dis 2001; 183: 113-118.
147 English M, Marsh V, Amukoye E. et al. Chronic salicylate poisoning and severe malaria. Lancet 1996; 347: 1736-1737.
148 Harizi H, Juzan M, Pitard V. et al. Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 2002; 168: 2255-2263.
149 Serirom S, Raharjo WH, Chotivanich K. et al. Anti-adhesive effect of nitric oxide on Plasmodium falciparum cytoadherence under flow. Am J Pathol 2003; 162: 1651-1660.
150 Pino P, Vouldoukis I, Dugas N. et al. Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum-infected erythrocytes. Cell Microbiol 2004; 06: 839-848.
151 Yeo TW, Lampah DA, Gitawati R. et al. Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. J Infect Dis 2008; 198: 602-608.
152 Combes V, Taylor TE, Juhan-Vague I. et al. Circulating endothelial microparticles in malawian children with severe falciparum malaria complicated with coma. Jama 2004; 291: 2542-2544.
153 Combes V, Simon AC, Grau GE. et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93-102.
154 Jy W, Jimenez JJ, Mauro LM. et al. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost 2005; 03: 1301-1308.
155 Perez-Casal M, Downey C, Fukudome K. et al. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 2005; 105: 1515-1522.
156 Perez-Casal M, Downey C, Cutillas-Moreno B. et al. Microparticle-associated endothelial protein C receptor and the induction of cytoprotective and anti-inflammatory effects. Haematologica 2009; 94: 387-394.
157 Ghosh A, Li W, Febbraio M. et al. Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in mice. J Clin Invest 2008; 118: 1934-1943.
158 Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008; 99: 480-486.
159 Hemmer CJ, Kern P, Holst FG. et al. Neither heparin nor acetylsalicylic acid influence the clinical course in human Plasmodium falciparum malaria: a prospective randomized study. Am J Trop Med Hyg 1991; 45: 608-612.