Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum-infected erythrocytes.
Cytoadherence of parasitized red blood cells (PRBCs) to postcapillary venules and cytokine production are clearly involved in the pathogenesis of cerebral malaria. Nitric oxide and TNF-alpha have been proposed as major effector molecules both in protective and physiopathological processes during malaria infections. Nitric oxide production has been shown to be induced by engagement of CD23 antigen. This study aimed to investigate the potential role of the CD23/nitric oxide pathway in the control of the cytoadherence of PRBCs on human endothelial cells. We demonstrate that normal human lung endothelial cells (HLECs) are able to express the low affinity receptor for IgE (Fc in RII/CD23), following cell incubation with interleukin 4 or PRBCs. Ligation of the CD23 antigen by a specific anti-CD23 monoclonal antibody at the cell surface of HLECs was found to induce iNOS mRNA and protein expression, NO release and P. falciparum killing. In addition, the specific CD23-engagement on these cells also induced a significant decrease in ICAM-1 expression, an adhesion molecule implicated in PRBCs cytoadherence. These data not only described for the first time the expression of a CD23 antigen at the cell surface of endothelial cells but also suggest a possible new regulatory mechanisms via the CD23/NO pathway during malaria infection.
Pino
Paco
P
INSERM U511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière Paris VI, 75013 Paris, France.
Vouldoukis
Ioannis
I
Dugas
Nathalie
N
Conti
Marc
M
Nitcheu
Josiane
J
Traore
Boubacar
B
Danis
Martin
M
Dugas
Bernard
B
Mazier
Dominique
D
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010963:Plasmodium falciparum / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*
D000962:Antimalarials; D012333:RNA, Messenger; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II