Molecular mechanisms and biological importance of Plasmodium falciparum erythrocyte rosetting.
Rosetting, i.e. the spontaneous binding of uninfected to malaria infected erythrocytes and endothelial cytoadherence may hinder the blood flow and lead to severe Plasmodium falciparum malaria. Falciparum isolates obtained from unconscious patients all form rosettes and/or express a significantly higher mean rosetting rate than isolates from patients with uncomplicated malaria. Furthermore, sera of patients with cerebral malaria are devoid of anti-rosetting activity while sera from patients with mild disease carry high levels of anti-rosetting antibodies. The presence of anti-rosetting antibodies also seems important for the efficient interaction of rosetting infected rbc and leukocytes. Two parasite derived rosetting ligands of Mr 22K and Mr 28K named "rosettins", have been found on the surface of rosetting infected erythrocytes. CD36 has in at least some strains of parasites been found to function as a rosetting receptor on the uninfected erythrocyte. Heparin disrupts rosettes of P. falciparum in vitro and inhibits the sequestration of rosetting cells ex vivo. In conclusion, rosetting seems a crucial factor in the development of cerebral malaria and treatment of patients with anti-rosetting substances might become an effective adjunct in the treatment of severe malaria.
Wahlgren
M
M
Department of Infectious Diseases, Karolinska Institutet, Huddinge Hospital, Sweden.
Carlson
J
J
Helmby
H
H
Hedlund
I
I
Treutiger
C J
CJ
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018955:CD36 Antigens; D002448:Cell Adhesion; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004730:Endothelium, Vascular / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology* / Q000648:ultrastructure; D006801:Humans; D016779:Malaria, Cerebral / Q000469:parasitology / Q000473:pathology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism; D012397:Rosette Formation
D015703:Antigens, CD; D018955:CD36 Antigens; D015800:Protozoan Proteins