Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acidin placental malaria

Infection with Plasmodium falciparum during pregnancy leads to the accumula tion of parasite-infected erythrocytes in the placenta(1), and is associate d with excess perinatal mortality, premature delivery and intrauterine grow th retardation in the infant, as well as increased maternal mortality and m orbidity(2,3). P. falciparum can adhere to specific receptors on host cells , an important virulence factor enabling parasites to accumulate in various organs(4). We report here that most P. falciparum isolates from infected p lacentae can bind to hyaluronic acid, a newly discovered receptor for paras ite adhesion that is present on the placental lining. In laboratory isolate s selected for specific high-level adhesion, binding to hyaluronic acid cou ld be inhibited by dodecamer or larger oligosaccharide fragments or polysac charides, treatment of immobilized receptor with hyaluronidase, or treatmen t of infected erythrocytes with trypsin. In vitro flow-based assays demonst rated that high levels of adhesion occurred at low wall shear stress, condi tions thought to prevail in the placenta. Our findings indicate that adhesi on to hyaluronic acid is involved in mediating placental parasite accumulat ion, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preven tative interventions.