Comparative study of the adhesion of sickle cells and malarial-parasitized red cells to cultured endothelium.
Increased adhesion of red cells to vascular endothelium has been implicated in the pathogenesis of falciparum malaria and sickle cell disease. We have carried out a comparative study of the adhesiveness of normal (AA), sickle trait (AS), and homozygous sickle (SS) red cells, with and without parasitization by Plasmodium falciparum, with an in vitro flow system. Adhesion of nonparasitized red cells to cultured human umbilical vein endothelial cells (either glutaraldehyde fixed or untreated) was strongly dependent on the wall shear stress. Many AA and SS cells adhered at low stress (0.02 Pa), but far fewer did so when the stress was increased to a physiologic level (0.1 Pa). Compared with AA cells, SS adhered in greater number (about threefold) and required greater stress (about two-fold) for their subsequent removal. In contrast, the efficiency of adhesion of AA cells parasitized by Plasmodium falciparum was essentially constant up to 0.1 Pa, where it was about 1000 times greater than the efficiency for nonparasitized cells. The stress required to remove parasitized cells was about 6 times that for controls. When parasites were grown in SS cells, fewer cells adhered than when parasites were grown in AA cells. However, the adhesion of malarial-parasitised AS cells was only slightly less than that of parasitized AA cells, so that modulation of adhesion is unlikely to underlie the protective effect of sickle gene in malaria. Adhesion of red cells to endothelium may promote blockage of microvessels, and the interaction of parasitized cells appears strong enough to directly cause ischemic complications in falciparum malaria.
Rowland
P G
PG
Department of Haematology, Medical School, University of Birmingham, UK.
Nash
G B
GB
Cooke
B M
BM
Stuart
J
J
D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology / Q000502:physiology*; D006801:Humans; D008833:Microcirculation; D010963:Plasmodium falciparum / Q000502:physiology*; D012805:Sickle Cell Trait / Q000097:blood*