Preparation of clinical grade proteins produced by recombinant DNA technologies

Takács, B.; Girard, M. F.

doi:10.1016/0022-1759(91)90048-k

Cited by 49 publications

(23 citation statements)

References 17 publications

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“…The Escherichia coli-derived CS27IVC represents the complete P. falciparum CS sequence from the T4 isolate, except that the hydrophobic NH 2 -and COOH-terminal amino acids 1-26 and 412-424 have been deleted, and 5 histidine residues have been added to the COOH terminus to facilitate purification (11). The recombinant protein used in these studies was kindly provided by Dr. Bela Takacs (Hoffmann-La Roche).…”

Section: Methodsmentioning

confidence: 99%

The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for PlasmodiumSporozoite Attachment to Target Cells

Pinzon-Ortiz¹,

Friedman²,

Esko³

et al. 2001

Journal of Biological Chemistry

117

120

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The major surface protein of malaria sporozoites, the circumsporozoite protein, binds to heparan sulfate proteoglycans on the surface of hepatocytes. It has been proposed that this binding event is responsible for the rapid and specific localization of sporozoites to the liver after their injection into the skin by an infected anopheline mosquito. Previous in vitro studies performed under static conditions have failed to demonstrate a significant role for heparan sulfate proteoglycans during sporozoite invasion of cells. We performed sporozoite attachment and invasion assays under more dynamic conditions and found a dramatic decrease in sporozoite attachment to cells in the presence of heparin. In contrast to its effect on attachment, heparin does not appear to have an effect on sporozoite invasion of cells. When substituted heparins were used as competitive inhibitors of sporozoite attachment, we found that sulfation of the glycosaminoglycan chains at both the Nand O-positions was important for sporozoite adhesion to cells. We conclude that the binding of the circumsporozoite protein to hepatic heparan sulfate proteoglycans is likely to function during sporozoite attachment in the liver and that this adhesion event depends on the sulfated glycosaminoglycan chains of the proteoglycans.Protozoans of the genus Plasmodium are the causative agents of malaria. Malaria infection is initiated when an infected anopheline mosquito injects sporozoites during a blood meal. The injected sporozoites travel to the liver and invade hepatocytes where they develop into exoerythrocytic forms. The speed and specificity of sporozoite localization to hepatocytes suggest a receptor-mediated event. Previous studies have shown that the major sporozoite surface protein, the circumsporozoite protein (CS), 1 binds to heparan sulfate proteogly- (3, 4). However, the inhibitory effect on sporozoite infectivity, while demonstrating that the CS-HSPG interaction is important, does not indicate if the glycan is required for sporozoite attachment, invasion, or subsequent development in hepatocytes.In vitro assays (5, 6) have been used to determine whether the CS-HSPG interaction is critical for cell invasion. Frevert et al. (6) found that removal of the majority of cell surface HSPGs had a minimal inhibitory effect on sporozoite invasion of cells. One interpretation of these data is that the binding of CS to HSPGs does not function during sporozoite invasion. Another possibility, however, is that CS binding to HSPGs functions in the more dynamic conditions found in the blood circulation and leads to arrest of sporozoites in the liver sinusoids. In this paper we modify the standard sporozoite invasion assay and provide evidence that the interaction between CS and cell surface HSPGs functions during the initial attachment of sporozoites to cells under conditions that mimic flow. In addition, we show that the sulfate moieties of the HSPG glycosaminoglycan chains (GAGs) are important for attachment of sporozoites to cells. MATERIALS AND METHODSSpo...

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Section: Methodsmentioning

confidence: 99%

The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for PlasmodiumSporozoite Attachment to Target Cells

Pinzon-Ortiz¹,

Friedman²,

Esko³

et al. 2001

Journal of Biological Chemistry

117

120

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“…CS protein, the Escherichia coli-derived recombinant CS27IVC [NANPNVDP]3[NANP]2~300-411), represents the complete Plasmodiumfalciparum CS sequence from the T4 isolate, except that the hydrophobic NH2-and COOH-terminal amino acids 1-26 and 412-424 have been deleted and five histidine residues have been added to the COOH terminus to facilitate purification (32). The recombinant protein used in these studies was generously provided by Dr. Bela Takacs (F. Hoffmann-La Roche Ltd., Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes.

Sinnis

Willnow

Briones

et al. 1996

The Journal of Experimental Medicine

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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.

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“…The Escherichia coli-derived recombinant CS27IVC represents the complete Plasmodium falciparum CS sequence from the T4 isolate, excepting the hydrophobic NH 2 -and COOHterminal amino acids (residues 1-26 and 412-424) and includes five histidine residues which were added to facilitate purification [9]. The recombinant CS used in these studies was kindly provided by Dr Bela Takacs (F. Hoffmann-La Roche, Basel, Switzerland).…”

Section: Recombinant Proteins Monoclonal Antibodies and Peptidesmentioning

confidence: 99%

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

Sidjanski

Vanderberg

Sinnis

1997

Molecular and Biochemical Parasitology

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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.

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Preparation of clinical grade proteins produced by recombinant DNA technologies

Cited by 49 publications

References 17 publications

The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for PlasmodiumSporozoite Attachment to Target Cells

The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for PlasmodiumSporozoite Attachment to Target Cells

Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes.

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

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