Primary culture of human lung microvessel endothelial cells: a useful in vitro model for studying Plasmodium falciparum-infected erythrocyte cytoadherence.
In the past, several cell lines have been used as in vitro models for studying cytoadherence, which refers to the specific binding of Plasmodium falciparum-parasitized red blood cells (PRBC) to host endothelium of microvessels. These models include: (a) human cells, including human umbilical vein endothelial cells (HUVEC), C32 amelanotic melanoma cells and monocytes; (b) non-human cells transfected with human genes, including COS and CHO cells; and (c) purified candidate receptor molecules. However, endothelial cells from malaria target organs are rarely investigated. In this study, we describe the efficient isolation and characterization of human lung endothelial cells (HLEC). This is the first in vitro study of P. falciparum PRBC cytoadherence to human lung endothelium, one of the target organs during severe malaria. The endothelial nature of the HLEC lines was confirmed by the presence of the von Willebrand factor, anti-human platelet endothelial adhesion molecule-1 and E-selectin antigens as specific endothelial markers. After exposure of HLEC to human cytokines, FACScan analysis indicated the coexpression of PRBC receptors CD36, intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The laboratory-adapted P. falciparum strains adhered specifically in vitro to these HLEC. The binding of PRBC could be inhibited with variable efficiency by various monoclonal antibodies (anti-CD36 > anti-ICAM-1 > anti-VCAM-1 > anti-E-selectin). Target organ specific cell lines such as HLEC expressing a variety of potential P. falciparum PRBC cytoadherence receptors may provide in vitro systems for studying the pathophysiology of severe malaria and identifying new therapeutic agents designed to directly block adhesive events involved in severe malaria.
Muanza
K
K
Département des Maladies Infectieuses, Parasitaires, Tropicales et de Santé Publique, INSERM U 313, Groupe Hospitalier Pitié-Salpêtrière, Paris.
Gay
F
F
Behr
C
C
Scherf
A
A
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D008833:Microcirculation / Q000166:cytology*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000472:pathogenicity*