A model for sequestration of the transmission stages of Plasmodium falciparum: Adhesion of gametocyte-infected erythrocytes to human bone marrow cells

With the aim of developing an appropriate in vitro model of the sequestrati on of developing Plasmodium falciparum sexual-stage parasites, we have inve stigated the cytoadherence of gametocytes to human bone marrow cells of str omal and endothelial origin. Developing stage III and IV gametocytes, but n ot mature stage V gametocytes, adhere to bone marrow cells in significantly higher densities than do asexual-stage parasites, although these adhesion densities are severalfold lower than those encountered in classical CD36-de pendent assays of P. falciparum cytoadherence, This implies that developing gametocytes undergo a transition from high-avidity, CD36-mediated adhesion during stages I and II to a lower-avidity adhesion during stages III and I V. We show that this adhesion is CD36 independent, fixation sensitive, stim ulated by tumor necrosis factor alpha, and dependent on divalent cations an d serum components, These data suggest that gametocytes and asexual parasit es utilize distinct sets of receptors for adhesion during development in th eir respective sequestered niches, To identify receptors for gametocyte-spe cific adhesion of infected erythrocytes to bone marrow cells, we tested a l arge panel of antibodies for the ability to inhibit cytoadherence, Our resu lts implicate ICAM-1, CD49c, CD166, and CD164 as candidate bone marrow cell receptors for gametocyte adhesion.