Mechanisms of cytoadhesion of flowing, parasitized red blood cells from Gambian children with falciparum malaria.
Adhesion of parasitized red blood cells to vascular endothelium is considered to be a major factor in the pathophysiology of falciparum malaria, and so the molecular mechanisms and rheologic characteristics of this interaction are of profound importance. We have investigated the adhesive behavior of wild-type parasite isolates cultured from the blood of Gambian children with falciparum malaria and allowed to flow over surfaces coated with formaldehyde-fixed human umbilical vein endothelial cells (HUVEC) or platelets. Parasitized cells were able to attach to HUVEC and/or to platelets, and studies with monoclonal antibodies showed that intercellular adhesion molecule-1 (ICAM-1) and CD36 antigen were the major mediators of adhesion for the two surfaces, respectively. The levels of adhesion to HUVEC and to platelets were highly variable but did not correlate with each other, so that different isolates express independently variable capacities to bind to the two receptors. Adhesion was stationary for platelets and generally at a higher level compared with binding to HUVEC, which was predominantly (about 60%) of a rolling type. The stationary component of adhesion to HUVEC represented a greater proportion of adhesion for the wild isolates than for laboratory-adapted strains, and this form of adhesion was relatively insensitive to antibody to ICAM-1. This suggests the existence of an additional endothelial cell-expressed receptor for the wild isolates. These studies show wide variation in the ability of wild isolates of Plasmodium falciparum to adhere to ICAM-1, CD36 antigen, and possibly other receptors in the presence of physiologically relevant flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Cooke
B M
BM
Department of Physiology, Medical School, University of Birmingham, United Kingdom.
Morris-Jones
S
S
Greenwood
B M
BM
Nash
G B
GB
D000818:Animals; D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D018955:CD36 Antigens; D002448:Cell Adhesion; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000302:isolation & purification / Q000502:physiology*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D015703:Antigens, CD; D018955:CD36 Antigens; D018799:Intercellular Adhesion Molecule-1