| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom;
Wellcome Trust Research Laboratories, College of Medicine, University of Malawi, Blantyre, Malawi;
Department of Microbiology and Immunology, MCP Hahnemann University School of Medicine, Philadelphia, PA 19129;
Institut National de la Santé et de la Recherche Médicale Unité 430, Hôpital Broussais, Paris, France;
¶ Kenya Medical Research Institute-Wellcome Trust Programme, KEMRI Centre for Geographical Medicine Research Coast, Kilifi, Kenya;
||
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
#
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110; and
**
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
The malaria parasite Plasmodium falciparum induces a number of novel adhesion properties in the erythrocytes that it infects. One of these properties, the ability of infected erythrocytes to bind uninfected erythrocytes to form rosettes, is associated with severe malaria and may play a direct role in the pathogenesis of disease. Previous work has shown that erythrocytes deficient in complement receptor (CR) 1 (CR1, CD35; C3b/C4b receptor) have greatly reduced rosetting capacity, indicating an essential role for CR1 in rosette formation. Using deletion mutants and mAbs, we have localized the region of CR1 required for the formation of P. falciparum rosettes to the area of long homologous repeat regions B and C that also acts as the binding site for the activated complement component C3b. This result raises the possibility that C3b could be an intermediary in rosetting, bridging between the infected erythrocyte and CR1. We were able to exclude this hypothesis, however, as parasites grown in C3-deficient human serum formed rosettes normally. We have also shown in this report that rosettes can be reversed by mAb J3B11 that recognizes the C3b binding site of CR1. This rosette-reversing activity was demonstrated in a range of laboratory-adapted parasite strains and field isolates from Kenya and Malawi. Thus, we have mapped the region of CR1 required for rosetting and demonstrated that the CR1-dependent rosetting mechanism occurs commonly in P. falciparum isolates, and could therefore be a potential target for future therapeutic interventions to treat severe malaria.
This article has been cited by other articles:
|
|
 |
|
  A. Ghumra, J.-P. Semblat, R. S. McIntosh, A. Raza, I. B. Rasmussen, R. Braathen, F.-E. Johansen, I. Sandlie, P. K. Mongini, J. A. Rowe, et al. Identification of Residues in the C{micro}4 Domain of Polymeric IgM Essential for Interaction with Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) J. Immunol., August 1, 2008; 181(3): 1988 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Normark, D. Nilsson, U. Ribacke, G. Winter, K. Moll, C. E. Wheelock, J. Bayarugaba, F. Kironde, T. G. Egwang, Q. Chen, et al. PfEMP1-DBL1{alpha} amino acid motifs in severe disease states of Plasmodium falciparum malaria PNAS, October 2, 2007; 104(40): 15835 - 15840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Kyes, S. M. Kraemer, and J. D. Smith Antigenic Variation in Plasmodium falciparum: Gene Organization and Regulation of the var Multigene Family Eukaryot. Cell, September 1, 2007; 6(9): 1511 - 1520. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Luginbuhl, M. Nikolic, H. P. Beck, M. Wahlgren, and H. U. Lutz Complement Factor D, Albumin, and Immunoglobulin G Anti-Band 3 Protein Antibodies Mimic Serum in Promoting Rosetting of Malaria-Infected Red Blood Cells Infect. Immun., April 1, 2007; 75(4): 1771 - 1777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Soares, D. L. Gerloff, N. R. Syme, A. F.W. Coulson, J. Parkinson, and P. N. Barlow Large-scale modelling as a route to multiple surface comparisons of the CCP module family Protein Eng. Des. Sel., August 1, 2005; 18(8): 379 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. MIBEI, A. S. S. ORAGO, and J. A. STOUTE IMMUNE COMPLEX LEVELS IN CHILDREN WITH SEVERE PLASMODIUM FALCIPARUM MALARIA Am J Trop Med Hyg, May 1, 2005; 72(5): 593 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Cockburn, M. J. Mackinnon, A. O'Donnell, S. J. Allen, J. M. Moulds, M. Baisor, M. Bockarie, J. C. Reeder, and J. A. Rowe From The Cover: A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria PNAS, January 6, 2004; 101(1): 272 - 277. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
