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Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes

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Item Type:Article
Title:Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes
Creators Name:Sinnis, P. and Willnow, T.E. and Briones, M.R. and Herz, J. and Nussenzweig, V.
Abstract:Remnants of lipoproteins, intestinal chylomicrons, and very low density lipoprotein (VLDL), are rapidly cleared from plasma and enter hepatocytes. It has been suggested that remnant lipoproteins are initially captured in the space of Disse by heparan sulfate proteoglycans (HSPGs), and that their subsequent internalization into hepatocytes is mediated by members of the LDL-receptor gene family. Similarly to lipoprotein remnants, malaria sporozoites are removed from the blood circulation by the liver within minutes after injection by Anopheles mosquitoes. The sporozoite's surface is covered by the circumsporozoite protein (CS), and its region II-plus has been implicated in the binding of the parasites to glycosaminoglycan chains of hepatocyte HSPGs. Lactoferrin, a protein with antibacterial properties found in breast milk and neutrophil granules, is also rapidly cleared from the circulation by hepatocytes, and can inhibit the hepatic uptake of lipoprotein remnants. Here we provide evidence that sporozoites, lactoferrin, and remnant lipoproteins are cleared from the blood by similar mechanisms. CS, lactoferrin, and remnant lipoproteins compete in vitro and in vivo for binding sites on liver cells. The relevance of this binding event for sporozoite infectivity is highlighted by our demonstration that apoliprotein E-enriched beta-VLDI and lactoferrin inhibit sporozoite invasion of HepG2 cells. In addition, malaria sporozoites are less infective in LDL-receptor knockout (LDLR -/-) mice maintained on a high fat diet, as compared with littermates maintained on a normal diet. We conclude that the clearance of lipoprotein remnants and sporozoites from the blood is mediated by the same set of highly sulfated HSPGs on the hepatocyte plasma membrane.
Keywords:Anopheles, Apolipoproteins E, Heparan Sulfate Proteoglycans, Heparitin Sulfate, Lactoferrin, Lipoproteins, VLDL Lipoproteins, Liver, Malaria, Plasmodium, Proteoglycans, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press
Volume:184
Number:3
Page Range:945-954
Date:1 September 1996
Additional Information:Copyright (c) 1996 by The Rockefeller University Press
Official Publication:http://www.jem.org/cgi/content/abstract/184/3/945
PubMed:View item in PubMed

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