1921
Volume 80, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 /VEGFR2 and CD34 /CD133 cells and plasma levels of the chemokine stromal cell–derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 /VEGFR2 and CD34 /CD133 cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2009.80.541
2009-04-01
2018-12-13
Loading full text...

Full text loading...

/deliver/fulltext/14761645/80/4/0800541.html?itemId=/content/journals/10.4269/ajtmh.2009.80.541&mimeType=html&fmt=ahah

References

  1. Turner G, 1997. Cerebral malaria. Brain Pathol 7 : 569–582. [Google Scholar]
  2. Newton CR, Taylor TE, Whitten RO, 1998. Pathophysiology of fatal falciparum malaria in African children. Am J Trop Med Hyg 58 : 673–683. [Google Scholar]
  3. Pongponratn E, Turner GD, Day NP, Phu NH, Simpson JA, Stepniewska K, Mai NT, Viriyavejakul P, Looareesuwan S, Hien TT, Ferguson DJ, White NJ, 2003. An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. Am J Trop Med Hyg 69 : 345–359. [Google Scholar]
  4. MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA, 1985. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119 : 385–401. [Google Scholar]
  5. Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10 : 143–145. [Google Scholar]
  6. Adams S, Brown H, Turner G, 2002. Breaking down the blood-brain barrier: signaling a path to cerebral malaria? Trends Parasitol 18 : 360–366. [Google Scholar]
  7. Brown H, Hien TT, Day N, Mai NT, Chuong LV, Chau TT, Loc PP, Phu NH, Bethell D, Farrar J, Gatter K, White N, Turner G, 1999. Evidence of blood-brain barrier dysfunction in human cerebral malaria. Neuropathol Appl Neurobiol 25 : 331–340. [Google Scholar]
  8. Combes V, Taylor TE, Juhan-Vague I, Mege JL, Mwenechanya J, Tembo M, Grau GE, Molyneux ME, 2004. Circulating endothelial microparticles in Malawian children with severe falciparum malaria complicated with coma. JAMA 291 : 2542–2544. [Google Scholar]
  9. Muanza K, Traore B, Gay F, Krudsood S, Danis M, Looareesuwan S, 1999. Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand. Ann Trop Med Parasitol 93 : 449–455. [Google Scholar]
  10. Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, Day NP, White NJ, Berendt AR, 1998. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal micro-vascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 152 : 1477–1487. [Google Scholar]
  11. Horstmann RD, Dietrich M, 1985. Haemostatic alterations in malaria correlate to parasitaemia. Blut 51 : 329–335. [Google Scholar]
  12. Mohanty D, Ghosh K, Nandwani SK, Shetty S, Phillips C, Rizvi S, Parmar BD, 1997. Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria. Am J Hematol 54 : 23–29. [Google Scholar]
  13. de Mast Q, Groot E, Lenting PJ, de Groot PG, McCall M, Sauerwein RW, Fijnheer R, van der Ven A, 2007. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis 196 : 622–628. [Google Scholar]
  14. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM, 1997. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275 : 964–967. [Google Scholar]
  15. Urbich C, Dimmeler S, 2004. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95 : 343–353. [Google Scholar]
  16. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP, 2000. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105 : 71–77. [Google Scholar]
  17. Rafii S, 2000. Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 105 : 17–19. [Google Scholar]
  18. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T, 2003. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348 : 593–600. [Google Scholar]
  19. Hristov M, Erl W, Weber PC, 2003. Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 23 : 1185–1189. [Google Scholar]
  20. Mutunga M, Fulton B, Bullock R, Batchelor A, Gascoigne A, Gillespie JI, Baudouin SV, 2001. Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med 163 : 195–200. [Google Scholar]
  21. Rosenzweig A, 2003. Endothelial progenitor cells. N Engl J Med 348 : 581–582. [Google Scholar]
  22. Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP, 1997. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med 337 : 1584–1590. [Google Scholar]
  23. Sowemimo-Coker SO, Meiselman HJ, Francis RB Jr, 1989. Increased circulating endothelial cells in sickle cell crisis. Am J Hematol 31 : 263–265. [Google Scholar]
  24. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T, 1999. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5 : 434–438. [Google Scholar]
  25. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S, 2001. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89 : E1–E7. [Google Scholar]
  26. Woywodt A, Streiber F, de Groot K, Regelsberger H, Haller H, Haubitz M, 2003. Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet 361 : 206–210. [Google Scholar]
  27. Heeschen C, Lehmann R, Honold J, Assmus B, Aicher A, Walter DH, Martin H, Zeiher AM, Dimmeler S, 2004. Profoundly reduced neovascularization capacity of bone marrow mononu-clear cells derived from patients with chronic ischemic heart disease. Circulation 109 : 1615–1622. [Google Scholar]
  28. Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM, 2005. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111 : 2981–2987. [Google Scholar]
  29. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G, 2005. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353 : 999–1007. [Google Scholar]
  30. Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S, 2000. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95 : 952–958. [Google Scholar]
  31. Salven P, Mustjoki S, Alitalo R, Alitalo K, Rafii S, 2003. VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood 101 : 168–172. [Google Scholar]
  32. WHO, 1990. Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg 84 (Suppl 2): 1–65. [Google Scholar]
  33. Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S, 2001. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 103 : 2885–2890. [Google Scholar]
  34. Kurtzhals JA, Rodrigues O, Addae M, Commey JO, Nkrumah FK, Hviid L, 1997. Reversible suppression of bone marrow response to erythropoietin in Plasmodium falciparum malaria. Br J Haematol 97 : 169–174. [Google Scholar]
  35. Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T, 2003. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for isch-emic neovascularization. Circulation 107 : 1322–1328. [Google Scholar]
  36. Shao H, Tan Y, Eton D, Yang Z, Uberti MG, Li S, Schulick A, Yu H, 2008. Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels. Stem Cells 26 : 1376–1384. [Google Scholar]
  37. Kopp HG, Ramos CA, Rafii S, 2006. Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of tumor and ischemic tissue. Curr Opin Hematol 13 : 175–181. [Google Scholar]
  38. Marsh K, Snow RW, 1997. Host-parasite interaction and morbidity in malaria endemic areas. Philos Trans R Soc Lond B Biol Sci 352 : 1385–1394. [Google Scholar]
  39. Greenwood B, Marsh K, Snow R, 1991. Why do some African children develop severe malaria? Parasitol Today 7 : 277–281. [Google Scholar]
  40. Khakoo AY, Finkel T, 2005. Endothelial progenitor cells. Annu Rev Med 56 : 79–101. [Google Scholar]
  41. Werner N, Nickenig G, 2006. Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy? Arterioscler Thromb Vasc Biol 26 : 257–266. [Google Scholar]
  42. Roncalli JG, Tongers J, Renault MA, Losordo DW, 2008. Endothelial progenitor cells in regenerative medicine and cancer: a decade of research. Trends Biotechnol 26 : 276–283. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2009.80.541
Loading
/content/journals/10.4269/ajtmh.2009.80.541
Loading

Data & Media loading...

  • Received : 10 Sep 2008
  • Accepted : 06 Nov 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error