Cytokine Upregulation of CD36, But Not ICAM-1, Increases Plasmodium Falciparum-Infected Erythrocyte Adherence to Microvascular Endothelial Cells under Shear Conditions
التفاصيل البيبلوغرافية
العنوان:
Cytokine Upregulation of CD36, But Not ICAM-1, Increases Plasmodium Falciparum-Infected Erythrocyte Adherence to Microvascular Endothelial Cells under Shear Conditions
Cytoadherence of parasitized red blood cells (PRBC) to microvascular endothelial cells (MEC) contributes to the pathogenesis of human cerebral malaria (MacPherson et al., 1985). We studied cytoadherence of two strains (HB3 and FC27) of Plasmodium falciparum PRBC to human MEC cultures under shear conditions to elucidate the pathways of adherence to MEC (Wick and Louis, 1991). Using antiICAM-1 and anti-CD36 antibodies, we found that HB3 PRBC bound exclusively to CD36 and ICAM-1 receptors. FC27 PRBC bound to MEC via CD36 (and at least one other pathway) but not to ICAM-1. Stimulation of MEC with interferon gamma (IFNy), which selectively increases CD36 expression, elevated HB3 and FC27 PRBC adherence 64% and 71%, respectively. Conversely, MEC stimulation with tumor necrosis factor (TNF), which selectively upregulates ICAM-1, did not increase HB3 PRBC adherence, in contrast to previous data using large vessel endothelium. Downregulation of CD36 and ICAM-1 expression by phorbol 12, 113-dibutyrate completely abolished HB3 PRBC adherence. These data suggest that cytoadherence to microvascular EC is distinct from adherence to large vessel EC (Berendt et aL, 1989). PRBC adherence to MEC is strain specific, regulatable by cytokines which increase CD36 expression, and abrogated by pharmacologic modulation of MEC receptors. These data have defined the relative contributions of both CD36 and ICAM-1 to PRBC binding to microvascular endothelium and have provided evidence for the presence of an additional adhesion mechanism. antibody therapy of pharmacological manipulation of endothelial cell receptor expression may reduce PBRC adherence to MEC and ameliorate the sequestration associated with human cerebral malaria.