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Infect Immun, June 1998, p. 2969-2975, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Multiple Adhesive Phenotypes Linked to Rosetting
Binding of Erythrocytes in Plasmodium falciparum
Malaria
Victor
Fernandez,1
Carl Johan
Treutiger,1
Gerard B.
Nash,2 and
Mats
Wahlgren1,*
Microbiology and Tumor Biology Center,
Karolinska Institutet, and Swedish Institute for Infectious Disease
Control, S-171 77 Stockholm, Sweden,1 and
Department of Physiology, University of Birmingham,
Birmingham B15 2TT, United Kingdom2
Received 8 December 1997/Returned for modification 5 February
1998/Accepted 13 March 1998
The cerebral form of severe malaria is associated with excessive
intravascular sequestration of Plasmodium
falciparum-infected erythrocytes (PRBC). Retention and
accumulation of PRBC may lead to occlusion of brain microvessels and
direct the triggering of acute pathologic changes. Here we report that
by selection, cloning, and subcloning, we have identified rare P. falciparum parasites expressing a pan-adhesive phenotype linked
to erythrocyte rosetting, a previously identified correlate of cerebral
malaria. Rosetting PRBC not only bound uninfected erythrocytes
but also formed autoagglutinates, adhered to endothelial cells, and
bound to CD36, immunoglobulins, and the blood group A antigen. The
linkage of rosetting, autoagglutination, and cytoadherence involved the
coexpression on a single PRBC of ligands with multiple specificities
and the binding to two or more receptors on erythrocytes and to
at least two other cell adhesion molecules, including a new endothelial
cell receptor for P. falciparum-infected erythrocytes. Limited proteolysis that differentially cleaved the rosetting ligand PfEMP1 from the PRBC surface abrogated all the binding phenotypes of these parasites, implicating the variant antigen PfEMP1 as a carrier of multiple ligand
specificities. The results encourage the further study of pan-adhesion
as a potentially important parasite phenotype in the pathogenesis of
severe P. falciparum malaria.
*
Corresponding author. Mailing address: MTC, Karolinska
Institute, Box 280, 171 77 Stockholm, Sweden. Phone: 46 8 7287277. Fax:
46 8 331547. E-mail: mats.wahlgren{at}smi.ki.se.
Infect Immun, June 1998, p. 2969-2975, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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