Comparative study of the primary structures of sero-, lacto- and ovotransferrin glycans from different species

Spik, Geneviève; Coddeville, Bernadette; Montreuil, Jean

doi:10.1016/0300-9084(88)90283-0

Cited by 156 publications

(98 citation statements)

References 25 publications

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“…This indicates that a significant portion of Asn624 located at the C-lobe is glycosylated in P. pastoris compared with that of mammalian cells. It has been reported that Asn624 is not glycosylated in human milk and leukocyte LFs [13,32]. In addition, glycoengineered P. pastoris do not display core-fucosylation of N-linked glycans.…”

Section: Discussionmentioning

confidence: 95%

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Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response

et al. 2008

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Traditional production of therapeutic glycoproteins relies on mammalian cell culture technology. Glycoproteins produced by mammalian cells invariably display N-glycan heterogeneity resulting in a mixture of glycoforms the composition of which varies from production batch to production batch. However, extent and type of N-glycosylation has a profound impact on the therapeutic properties of many commercially relevant therapeutic proteins making control of N-glycosylation an emerging field of high importance. We have employed a combinatorial library approach to generate glycoengineered Pichia pastoris strains capable of displaying defined human-like N-linked glycans at high uniformity. The availability of these strains allows us to elucidate the relationship between specific N-linked glycans and the function of glycoproteins. The aim of this study was to utilize this novel technology platform and produce two human-like N-linked glycoforms of recombinant human lactoferrin (rhLF), sialylated and non-sialylated, and to evaluate the effects of terminal N-glycan structures on in vitro secondary humoral immune responses. Lactoferrin is considered an important first line defense protein involved in protection against various microbial infections. Here, it is established that glycoengineered P. pastoris strains are bioprocess compatible. Analytical protein and glycan data are presented to demonstrate the capability of glycoengineered P. pastoris to produce fully humanized, active and immunologically compatible rhLF. In addition, the biological activity of the rhLF glycoforms produced was tested in vitro revealing the importance of N-acetylneuraminic (sialic) acid as a terminal sugar in propagation of proper immune responses.

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Section: Discussionmentioning

confidence: 95%

“…Human LF glycans are the N-acetyllactosaminic type, α1-3-fucosylated on the Nacetylglucosamine residue linked to the peptide chain. Unlike the milk-derived LF, the neutrophilic form is not fucosylated, and the difference in molecular structure and function of the two forms is not fully understood [23,32].…”

Section: Introductionmentioning

confidence: 99%

Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response

et al. 2008

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“…HLf and BLf share similar amino acid sequences and structures (Pierce et al, 1991). However, BLf has four potential N-linked glycosylation sites, of which two to three have been shown to be occupied by high-mannose-type oligosaccharides, whereas natural HLf has two N-acetyl-lactosaminic-type oligosaccharides (Coddeville et al, 1992;Spik et al, 1988;van Berkel et al, 1996). Based on these different glycosylation patterns, BLf and HLf may interact with different carbohydrate-binding receptors.…”

Section: Lf-binding Receptors Expressed On Dcs and Monocytesmentioning

confidence: 99%

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

Adams

Bond

Havenga

et al. 2009

Journal of General Virology

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The coxsackievirus-adenovirus receptor (CAR) is the described primary receptor for adenovirus serotype 5 (Ad5), a common human pathogen that has been exploited as a viral vector for gene therapy and vaccination. This study showed that monocytes and dendritic cells (DCs), such as freshly isolated human blood myeloid DCs, plasmacytoid DCs and monocyte-derived DCs, are susceptible to recombinant Ad5 (rAd5) infection despite their lack of CAR expression. Langerhans cells and dermal DCs from skin expressed CAR, but blocking CAR only partly decreased rAd5 infection, together suggesting that other receptor pathways mediate viral entry of these cells. Lactoferrin (Lf), an abundant protein in many bodily fluids known for its antiviral and antibacterial properties, promoted rAd5 infection in all cell populations except plasmacytoid DCs using a CAR-independent process. Lf caused phenotypic differentiation of the DCs, but cell activation played only a minor role in the increase in infection frequencies. The C-type lectin receptor DC-SIGN facilitated viral entry of rAd5-Lf complexes and this was dependent on highmannose-type N-linked glycans on Lf. These results suggest that Lf present at high levels at mucosal sites can facilitate rAd5 attachment and enhance infection of DCs. A better understanding of the tropism and receptor mechanisms of Ad5 may help explain Ad5 pathogenesis and guide the engineering of improved rAd vectors. INTRODUCTIONAdenoviruses are frequent causes of acute upper respiratory tract infections and can be responsible for ocular and gastrointestinal illnesses in humans. They have also been exploited for the development of replication-incompetent viral vectors because their genomes allow large inserts of expression cassettes, thereby offering efficient gene delivery. Recombinant adenoviruses (rAds), serotype 5 (rAd5) in particular, are commonly used vectors for gene therapy and vaccination trials (Barouch & Nabel, 2005;McConnell & Imperiale, 2004;Tatsis & Ertl, 2004). The primary receptor described for infection of most Ad species (A, C, D, E and F) is the coxsackievirus and adenovirus receptor (CAR) (Bergelson et al., 1997;Roelvink et al., 1998;Tomko et al., 1997). As currently understood, infection of Ad5 (species C) involves binding of the viral fiber knob to CAR on the target cells (Roelvink et al., 1996), followed by an interaction between the viral penton base with a v integrins on the cell surface (Wickham et al., 1993). This allows virus-receptor complexes to enter clathrin-coated pits via endocytosis Wang et al., 1998;Wickham et al., 1993). Efficient infection of Ad5 via CAR has mainly been demonstrated in vitro using immortalized cell lines with well-exposed CAR. However, CAR is naturally expressed in tight junctions between cells and therefore et al., 2007). In this study, we investigated the involvement of CAR and the influence of Lf in rAd5 infection in relevant primary human APC populations from both blood and skin. METHODSIsolation of blood DCs. This study was approved by the ethical commi...

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“…However, these glycoproteins differ in the number, the structure and the location of their glycans [9][10][11][12]. Otherwise, these transferrins bind to different cells such as reticulocytes (serotransferrin) [131, enterocytes (lactotransferrin) [14,15] and chick embryo red blood cells (ovotransferrin) [16], thus suggesting that specific transferrin receptors are present at the surface of these cells and recognize a glycan, a peculiar region of the polypeptide chain, or both.…”

Section: Introductionmentioning

confidence: 99%

The N‐terminal domain I of human lactotransferrin binds specifically to phytohemagglutinin‐stimulated peripheral blood human lymphocyte receptors

et al. 1989

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Human lactotransferrin receptors have been recently characterized on mitogen-stimulated human lymphocytes [(1989) Eur. J. Biochem. 179, 481-487]. In order to define the lactotransferrin recognition site by these receptors, the binding to lymphocytes of several tryptic fragments, isolated from human lactotransferrin by mild tryptic hydrolysis [(1984) Biochim. Biophys. Acta 787, 90-96]; has been investigated. The 30 kDa N-tryptic fragment (residues 4-281) and the re-associated N,C-tryptic complex bind to lactotansferrin lymphocyte receptor with a dissociation constant of 44 nM and 39 nM, respectively, similar to the value obtained for the native lactotransferrin (Kd = 46 riM). However, neither the N-terminal domain II (residues 91-257) nor the 50 kDa C-tryptic fragment (residues 282-703) are recognized. These results suggest that the binding site of human lactotransferrin by the lymphocyte receptor is located in the N-terminal lobe and more precisely in the N-terminal domain I (residues 4-90 and/or 258-281).

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Comparative study of the primary structures of sero-, lacto- and ovotransferrin glycans from different species

Cited by 156 publications

References 25 publications

Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response

Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

The N‐terminal domain I of human lactotransferrin binds specifically to phytohemagglutinin‐stimulated peripheral blood human lymphocyte receptors

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