Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum-infected erythrocytes

Abstract

SummaryCytoadherence 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-a a a a 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 OE OE OE OE 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.

Low levels of mammalian TGF-β1 are protective against malaria parasite infection, a paradox clarified in the mosquito host

“…Most studies to date have associated inducible NO production in the mammalian host with anti-parasitic effects (Rockett et al, 1991, Naotunne et al, 1993, Mellouk et al, 1994, Anstey et al, 1996, Pino et al, 2004, Sharma et al, 2004 as well as with increased inflammatory pathology to the host Cowden, 2003 andRiley et al, 2006). In contrast, two studies have concluded that higher levels of NO in humans (Hobbs et al, 2002) and in mice (Gramaglia et al, 2006) were associated with less severe malaria but no differences in parasitemia levels.…”

Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

“…On the other hand, the transmigration of THP-1 cells was reduced only when VCAM-1 or both ICAM-1 and VCAM-1 were blocked [34]. Similarly, a large panel of molecules is involved in the adhesion of IRBC on EC, including PECAM-1, CD36, chondroitin-sulphate A, ICAM-1, thrombospondin, αvβ3 E-selectin, P-selectin, and VCAM-1 [35]–[36]. The data we obtained for the two different parasite strains; 3Ci (which binds ICAM-1 and CD36) and CS2 (which mainly binds chondroitin-sulphate A), illustrates this diversity of these interactions.…”

Estradiol, but Not Dehydroepiandrosterone, Decreases Parasitemia and Increases the Incidence of Cerebral Malaria and the Mortality in <i>Plasmodium berghei</i> ANKA-Infected CBA Mice

“…Other studies revealed no correlation with disease progression [37,38] or even a protective role for NO [39,40] . Pino et al [41] showed that induction of NO via crosslinking of CD23 in lung endothelial cells decreases cytoadherence and mediates killing of P. falciparum , suggesting a protective role for NO. Data obtained in mice in general do not support a role for NO in CM pathology.…”