Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.

Abstract:

:Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.

journal_name

Nat Med

journal_title

Nature medicine

authors

Beeson JG,Rogerson SJ,Cooke BM,Reeder JC,Chai W,Lawson AM,Molyneux ME,Brown GV

doi

10.1038/71582

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

86-90

issue

1

eissn

1078-8956

issn

1546-170X

journal_volume

6

pub_type

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