Adherence of Plasmodium falciparum infected erythrocytes to CHO-745 cells and inhibition of binding by protein A in the presence of human serum.

Adhesion of erythrocytes infected with the malaria parasite Plasmodium falciparum to human host receptors is a process associated with severe malarial pathology. A number of in vitro cell lines are available as models for these adhesive processes, including Chinese hamster ovary (CHO) cells which express the placental adhesion receptor chondroitin-4-sulphate (CSA) on their surface. CHO-745 cells, a glycosaminoglycan-negative mutant CHO cell line lacking CSA and other reported P. falciparum adhesion receptors, are often used for recombinant expression of host receptors and for receptor binding studies. In this study we show that P. falciparum-infected erythrocytes can be easily selected for adhesion to an endogenous receptor on the surface of CHO-745 cells, bringing into question the validity of using these cells as a tool for P. falciparum adhesin expression studies. The adhesive interaction between CHO-745 cells and parasitized erythrocytes described here is not mediated by the known P. falciparum adhesion receptors CSA, CD36, or ICAM-1. However, we found that CHO-745-selected parasitized erythrocytes bind normal human IgM and that adhesion to CHO-745 cells is inhibited by protein A in the presence of serum, but not in its absence, indicating a non-specific inhibitory effect. Thus, protein A, which has been used as an inhibitor for a recently described interaction between infected erythrocytes and the placenta, may not be an appropriate in vitro inhibitor for understanding in vivo adhesive interactions.

A human schwannoma cell line supports the in vitro adhesion of Plasmodium falciparum infected erythrocytes to chondroitin-4-sulfate.

The paucity of human cell lines expressing defined receptors for the cytoadhesion of erythrocytes infected with the human malarial parasite Plasmodium falciparumhas hampered the investigation of this important virulence property. Here, we investigate a permanent cell line derived from a human, malignant schwannoma, termed HMS-97, and show that this cell line expresses chondroitin-4-sulfate as the only surface receptor to which P. falciparum-infected erythrocytes can cytoadhere. Other common receptors for parasite adhesion, including CD36, vascular cellular adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM-1), and E-selectin are absent. Thus, HMS-97 cells are a useful tool for the study of P. falciparum adhesion to chondoitin-4-sulfate, the main receptor for parasite sequestration in the placenta. As chondoitin-4-sulfate can be readily cleaved from the cells, HMS-97 cells are also an ideal system for expressing recombinant adhesion receptors and studying their function in binding assays.