The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of plasmodium falciparum sporozoites

Molecular and Biochemical Parasitology

1997

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In the mosquito, Plasmodium sporozoites rupture from oocysts found on the midgut wall, circulate in the hemolymph and invade salivary glands where they wait to be injected into a vertebrate host during a bloodmeal. The mechanisms by which sporozoites specifically attach to and invade salivary glands are not known but evidence suggests that it is a receptor-mediated process. Here we show that the major surface protein of sporozoites, the circumsporozoite protein (CS), binds preferentially to salivary glands when compared to other organs exposed to the circulating hemolymph. In addition, we show that a peptide encompassing region I, a highly conserved sequence found in all rodent and primate Plasmodium CS proteins, inhibits binding of CS to mosquito salivary glands.

Section: Discussionmentioning

confidence: 55%

Anopheles stephensi salivary glands bear receptors for region I of the circumsporozoite protein of Plasmodium falciparum

Sidjanski

Vanderberg

Molecular and Biochemical Parasitology

1997

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“…This was performed as described (39,40) with modifications as described (21). Briefly, HepG2 cells were plated in chamber slides, grown for 2 d, and incubated for 15 rain with each inhibitor before 50,000 P. berr sporozoites were added to each well.…”

Section: Methodsmentioning

confidence: 99%

“…Lactoferrin (aa [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] CAVS QPETKCFQRNMRKI/R yoelii CS, apoE, and lactoferrin. Boldface italics indicate amino acid residues of CS protein required for binding to HSPGs (22).…”

Section: Rklrkrllrdaedlqkrla Vmentioning

confidence: 99%

“…Heparinase treatment of liver sections that have been incubated with CS, and other in vitro experiments using hepatocytes and HepG2 cells as targets, demonstrate that CS binds to HSPGs (19,20). The proteoglycan-binding portion of CS (19,21) is region II-plus (22), a stretch of amino acids highly conserved in all species of malaria parasites (23). The region II-plus motif is also found in thrombospondin-related adhesive protein/sporozoite surface protein 2 (TRAP/ SSP2), another surface protein of malaria sporozoites (24,25) that binds to cell surface HSPGs (26,27).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes.

The Journal of Experimental Medicine

Willnow

Briones

et al. 1996

SummaryRemnants oflipoproteins, intestinal chylomicrons, and very low density lipoproteins (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 LDLreceptor 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 [3-VLDL 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 oflipoprotein remnants and sporozoites from the blood is mediated by the same set of highly sulfated HSPGs on the hepatocyte plasma membrane.

“…Several lines of evidence suggest that this arrest is mediated by the interaction between the major surface protein of sporozoites, the circumsporozoite protein (CSP) and the highly sulfated HSPGs of hepatocytes [35][36][37][38][39]. Recombinant CSP binds specifically to hepatic HSPGs and in vivo, the physiologic ligands for hepatic HSPGs, namely lactoferrin and lipoprotein remnants, delay CSP clearance from the circulation and inhibit sporozoite infection of hepatocytes [40].…”

Section: To the Livermentioning

confidence: 99%

A long and winding road: The Plasmodium sporozoite's journey in the mammalian host

Parasitology International

Coppi

2007

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