Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.
The clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, Plasmodium falciparum. We now report that a primary P. falciparum-infected erythrocyte (parasitized red blood cell [PRBC]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor alpha (TNF-alpha)-activated human vascular endothelial cells is partially inhibited by antibodies to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive. PRBCs selected in vitro by sequential panning on purified adhesion molecules bind concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes. These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and may help delineate alternative adhesion pathways PRBCs use to modify malaria pathology.
Ockenhouse
C F
CF
Immunology Branch, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington DC 20307.
Tegoshi
T
T
Maeno
Y
Y
Benjamin
C
C
Ho
M
M
Kan
K E
KE
Thway
Y
Y
Win
K
K
Aikawa
M
M
Lobb
R R
RR
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D016778:Malaria, Falciparum / Q000097:blood*; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016023:Integrins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1