Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way

Adherence of erythrocytes infected with Plasmodium falciparum to microvascu lar endothelial cells (sequestration) is considered to play an important ro le in parasite virulence and pathogenesis, However, the real importance of sequestration for infection and disease has never been fully assessed. The absence of an appropriate in vivo model far sequestration has been a major barrier, We have examined the rodent malaria parasite Plasmodium chabaudi c habaudi AS in mice as a potential model. Erythrocytes infected with this pa rasite adhere in vitro to purified CD36, a critical endothelium receptor fo r binding P. falciparum-infected erythrocytes. P. c. chabaudi-infected eryt hrocytes adhere in vitro to endothelial cells in a gamma interferon-depende nt manner, suggesting the involvement of additional adhesion molecules in t he binding process, as is also the case with P. falciparum-infected cells. Furthermore, plasma or sera from infected and hyperimmune mice, respectivel y, have the ability to block binding of infected erythrocytes to endothelia l cells. In vivo, erythrocytes containing mature P. c. chabaudi parasites a re sequestered from the peripheral circulation. Sequestration is organ spec ific, occurring primarily in the liver, although intimate contact between i nfected erythrocytes and endothelial cells is also observed in the spleen a nd brain. The results are discussed in the context of the use of this model to study (i) the relationship between endothelial cell activation and the level of sequestration and (ii) the primary function of sequestration in ma laria infection.