The present paper describes concisely the expression and role of α(1,2)-linked fucose on some glycoconjugates as well as the detection, distribution and potential role of that glycotope on human soluble plasma and cellular fibronectins in addition to the expression on both normal and pathological amniotic fluid and seminal plasma fibronectins. The determination of α(1,2)fucosylated glycans is considered with respect to its usefulness as a potential clinically applicable biomarker in obstetrics to monitor pregnancy and in andrology to evaluate the ejaculate of infertile men and in vitro fertilization.

Introduction

Human FN (fibronectin) contains 5–9% carbohydrates, linked largely through N-glycosidic bonds and to a lesser degree through O-type (Figure 1). The extent and type of FN glycosylation and differences in the linkages of terminal monosaccharide residues such as sialic acid and fucose varies depending on the source tissue, cell type and physiological state of the individual from whom they were taken [14].

Scheme of FN domain arrangement and glycan expression

Figure 1
Scheme of FN domain arrangement and glycan expression

Series of segments I, II, and III (ovals, squares, and rectangles) arranged into the functional FN domains which are known to bind: (1) heparin and other glucosaminoglycans as well as fibrin, (2) collagen, (3) cell-surface receptors, (4) heparin and other glucosaminoglycans, (5) fibrin, and (6) C-terminal sequences containing two disulfide bridges which link two nearly identical FN polypeptides. Segments EDA (extra domain A), EDB (extra domain B) and the variable IIICS are marked by black filled rectangles. EDA and EDB may be present in cellular FN, but they are never present in plasma FN. The variable IIICS region is present in most cellular FN, but only one of the two subunits in a plasma FN dimer contains a variable sequence. The representative N- and O-glycans are shown by black asterisks and grey ovals respectively. Various forms of FN elicit the site-specific differences among attached glycans.

Figure 1
Scheme of FN domain arrangement and glycan expression

Series of segments I, II, and III (ovals, squares, and rectangles) arranged into the functional FN domains which are known to bind: (1) heparin and other glucosaminoglycans as well as fibrin, (2) collagen, (3) cell-surface receptors, (4) heparin and other glucosaminoglycans, (5) fibrin, and (6) C-terminal sequences containing two disulfide bridges which link two nearly identical FN polypeptides. Segments EDA (extra domain A), EDB (extra domain B) and the variable IIICS are marked by black filled rectangles. EDA and EDB may be present in cellular FN, but they are never present in plasma FN. The variable IIICS region is present in most cellular FN, but only one of the two subunits in a plasma FN dimer contains a variable sequence. The representative N- and O-glycans are shown by black asterisks and grey ovals respectively. Various forms of FN elicit the site-specific differences among attached glycans.

N- and O-glycans of FN

The majority of the carbohydrates are located in the gelatin- and cell-binding domains, whereas the heparin- and fibrin-binding domains do not appear to be glycosylated (Figure 1). There are seven potential N-glycosylation sites in human FN and the attached oligosaccharide structures have been established using MS, MALDI–MS (matrix-assisted laser-desorption ionization MS), TOF-MS (time-of-flight MS). Three of these (Asn430, Asn528 and Asn542) are located in the 2F2 and 8F1 modules of the collagen-binding domain of cellular FN, whereas plasma FN has on average only two N-linked glycans [57].

The N-glycan located in the second type 2 module (2F2) in the gelatin-binding domain of fibronectin is surrounded by a partially solvent-exposed hydrophobic cluster of two double-stranded antiparallel β-sheets of polypeptide [8]. Complete deglycosylation of the collagen domain reduces the thermal stability of the 8F1 module. Chemical-shift differences between the two glycoforms, related to the 8F1 and 9F1 modules, disturb the functional properties of gelatin binding. Moreover, cell attachment to FN influences the stability of the collagen and gelatin binding. It has been postulated that the N-glycosylation of this region confers FN stability and protects against proteolytic degradation [68].

In the cell-binding domain, three oligosaccharide-binding sites are identified, located at Asn877, Asn1007 and Asn1244. Moreover, a fourth site has been barely detected at Asn2108 by Tajiri et al. [5]. Jones et al. [9] have shown that the asparagine-linked oligosaccharides of fibronectin act as modulators of biological functions: a lack of oligosaccharides on FN markedly enhanced its ability to promote the adhesion and spreading of fibroblasts, and also resulted in increased affinity for gelatin.

The O-glycosylation sites have been detected by specific monoclonal antibodies or lectins in both the N- and C-terminal regions of the molecule and in the IIICS (type-III connecting segment) domain [10,11], at Thr278 in the connecting segment between the fibrin–heparin-binding and collagen-binding domains (Figure 1). For plasma FN, O-glycans are localized at either Thr2064 or Thr2065 in connecting strand 3 [5]. Synovial fluid FN has an extra O-glycosylation site that has been identified within a region directly adjacent to the C-terminus of the collagen-binding domain [1,12].

The O-glycan [α (2,3)-sialylated α-N-acetylgalactosamine] attached to the hexapeptide VTHPGY, in the variable region of alternative-spliced FN, forms an extra-domain commonly called the oncofetal IIICS epitope [5,10,13]. The quantitative evaluation of IIICS O-linked glycosylated FN is believed to be among the most effective markers for preterm delivery [14] and a valuable histological marker for the invasiveness of urothelial carcinoma of the urinary bladder [15]. The role of mucin-type O-glycan has not been elucidated. Tajiri et al. [5] have suggested that the O-glycans within a connecting segment might play a significant role in segregating the neighbouring domains and that they maintain the topology of FN and the domain functions.

Differences between plasma and cellular FN

There are remarkable specific differences between plasma and cellular FN regarding the number of antennae, their degree of sialylation and α(1,6)fucosylation on the innermost GlcNAc of the chitobiose core. Both types of FN can be N-glycosylated at seven glycosylation sites. However, plasma FN may lack some glycans [5]. The major N-glycan of both isoforms is a bi-antennary complex-type structure. Plasma FN contains sialic acid on all seven oligosaccharides and only two have the fucosylated glycans. Plasma-derived oligosaccharides at Asn1007 are bi- and tri-antennary, heavily sialylated and weakly fucosylated. In contrast, cellular FN has bi-antennary glycans, largely fucosylated, but weakly sialylated [5,16].

Amniotic fluid FN contains largely multiantennary and polylactosamine-type structures derived from fetal tissue and approximately twice the amount of carbohydrate as the plasma form. N-glycans of fetal FN are only partially sialylated, in contrast with the fully sialylated plasma fibronectin. Fetal and cellular FN contains α(2,3)-linked sialic acid glycoforms, whereas blood plasma FN shows α(2,6)-linked sialic acid at the terminal galactose residue of the bi-antennary chain in most cases [3,13]. Krusius et al. [17] reported that plasma FN contains four times less core O-glycan residues than amniotic fluid FN. The physiological role of FN carbohydrates is uncertain, although they appear to stabilize FN against hydrolysis and modulate its affinity to some substrates [17,18].

α(1,2)-linked fucose is absent in human plasma FN, but occurs in amniotic and seminal plasma FNs

The expression of α(1,2)fucosylated glycotope in soluble FN, found in some biological fluids, has been analysed by Kątnik-Prastowska and co-workers ([3], and E.M. Kratz, R. Faundez and I. Kątnik-Prastowska, unpublished work) using UEA-1 (Ulex europaeus agglutinin 1) [20]. In this sandwich-type lectin ELISA, a soluble glycoprotein was extracted from biological fluids using the appropriate antibodies, and glycotopes of the glycoprotein were subsequently quantified with biotinylated lectin. The method is suitable for monosaccharides terminally attached to glycoproteins, such as sialic acid and fucose residues. The lectin ELISA does not determine the ‘true’ amount of fucose or sialic acid on glycoconjugates, but allows the observation of the changes in the relative amount of glycotope exposed in the glycoprotein, e.g. during development, aging or disease. Such observations mimic similar types of interactions which may occur in vivo, e.g. between sugar-ligands and their specific receptors.

The expression of the α(1,2)-linked fucosylated glycotope of FN seems to be dependent on the site of FN synthesis. FN produced by hepatocytes and released into the blood lacks α(1,2)-linked fucose. This glycotope was not found in blood plasma FN from healthy non-pregnant and pregnant women [3], healthy young, middle aged and older individuals, Alzheimer's disease and vascular dementia patients [21], and rheumatoid arthritis patients [4]. In contrast, amniotic and seminal FN are heavily covered by α(1,2)fucosylated glycotopes ([3], and E.M. Kratz, R. Faundez and I. Kątnik-Prastowska, unpublished work). Both FNs are cell-derived forms which are synthesized locally in tissues by many cell types. Amniotic fluid FN is largely derived from placental, decidual and amnion cell synthesis. The α(1,2)fucosylated glycotopes appear in amniotic FN at the end of the second trimester or at the beginning of the third trimester. From weeks 28 to 40 of gestation the expression of α(1,2)-linked fucose in FN is dynamic and is found to increase approx. 10-fold, whereas during parturition, the level does not change [22].

Seminal plasma FN is presumed to be produced by the accessory sex glands and is secreted into the epididymal tubule, where it then becomes a component of the epididymal fluid and ejaculate. During the immediate post-ejaculatory phase the intact dimeric FN is degraded to fragments by prostatic kallikrein-like protease [2,23]. It is interesting that seminal plasma contains only those FN fragments which were derived from glycosylated cell- and collagen-binding domains. The non-glycosylated N- and Cterminal heparin- and fibrin-binding domains were not found in seminal plasma, being totally degraded during ejaculate liquefaction.

Alterations in the expression of α(1,2)-linked fucose in amniotic and seminal FNs

The relative amount of α(1,2)-linked fucose in amniotic FN increases significantly during post-date pregnancy. It may be proposed that the higher expression of the α(1,2)fucosylated glycotope at week 40 of pregnancy predicts complication owing to post-term parturition and/or delivery of the fetus with post-maturity syndrome [22]. In contrast, the significantly lower level of α(1,2)-linked fucose in amniotic and seminal FN was found to be associated with pregnancies complicated by intra-uterine infection [3] and with leukocytospermia (E.M. Kratz, R. Faundez and I. Kątnik-Prastowska, unpublished work) respectively. During inflammatory diseases, FN can be degraded by bacterial or host-generated proteinases and glycosidases. As expected, degradation products were detected in the amniotic samples taken from pregnancies complicated by intra-uterine infection and in leukocytospermic seminal plasma. The observed decreased amount of α(1,2)-linked fucose in amniotic and seminal FN is probably associated with glycan degradation by specific glycosidases or/and from the synthesis of the α(2,3)-sialylated-Lewis X determinant, which inhibits the transfer of α(1,2)-fucose [24]. Using an animal model, Chavan et al. [25] have demonstrated that increased sialylation and defucosylation of plasma proteins are early events in the acute-phase response.

The expression and role of α(1,2)-linked fucose

α(1,2)-Linked fucose containing structures are characteristic of normal human tissues. They appear on the blood group antigen H [Fucα(1,2)-Galβ] and related antigens, including difucosylated Lewis B [Fucα(1,2)Galβ(1,3)]-[Fucα(1,4)GlcNAcβ1-R] and Y [Fucα(1,2)Galβ(1,4)]-[Fucα(1,3)GlcNAcβ1-R] determinants. They are normally present on the surface of human erythrocytes, a variety of epithelial cells, e.g. cells of the gastrointestinal epithelia, the lower genitourinary tract, the ureter and the vagina [26], and on the surface of embryonic and uterine endometrial cells [27]. Moreover, this determinant has been also found on some pathological cells, such as ovarian [28] and colorectal [29] cancer cells. The α(1,2)-linked fucose glycotope is absent from soluble glycoproteins synthesized by hepatocytes; however, it has been found on some soluble glycoconjugates in saliva [30], amniotic fluid [31], seminal and plasma glycoproteins [3234], and most human-milk oligosaccharides [35].

The fucose-containing molecules are ‘natural ligands’, critically important for cell-surface carbohydrate-binding proteins, i.e. cell-surface lectins. They mediate cell-recognition and adhesion-signalling pathways. For example, bifucosylated Lewis Y oligosaccharide, similar to other adhesion molecules, not only participates in the cell recognition and adhesion at the fetal/maternal interface during embryo implantation, up-regulating the DAG (diacylglycerol)/PKC (protein kinase C) signalling pathway in human endometrial cells [27], but also acts as a regulator of the expression of some other implantation-related molecules [36]. Moreover, evidence suggests that α(1,2)fucosylation plays a significant role in cognitive processes such as learning and memory, being involved in structural remodelling events that contribute to synaptic plasticicity, neuronal growth and regeneration [37,38].

Glycoconjugates containing α(1,2)-linked fucose in the gastric mucosa are known to play a crucial role in host–pathogen interactions. They provide an attachment ligand for some pathogen receptors playing a critical role in tissue colonization by pathogens. As they are present on the pathogens themselves, they stimulate an antibody response to these structures in the host. For example, the gastric pathogen Helicobacter pylori is capable of attachment to the gastric epithelium via host expression of the Lewis B antigen, a structure containing α(1,2)- and α(1,4)-linked fucose that is synthesized by the concerted action of the Se and Lewis (FUT3) fucosyltransferases [26]. On the other hand, expression of fucosylated Lewis-related structures, such as Lewis X, Lewis Y and Lewis B by H. pylori may induce autoimmune-mediated damage to the gastric epithelium, leading to chronic gastritis in a subset of H. pylori-induced humans [39]. Cervical mucins carry multiple α(1,2)fucosylated glycans which are ligands for opportunistic Candida albicans. Any perturbation in the vaginal flora allows this opportunistic organism to multiply, leading to symptomatic infection. There is a loss of α(1,2)fucosylated glycans in the mucosal secretions of ‘non-secretors’, where the lack of glycosyltransferase is associated with a 2.4–4.4-fold increased relative risk for recurrent vaginitis, urinary tract infection or oral candidiasis [40]. Human-milk oligosaccharides, which include glycans terminated by α(1,2)fucosyl residues, are known to protect infants against enteric pathogens, such as Campylobacter and Calicivirus [41].

The potential role of soluble FN decorated by α(1,2)-linked fucose

FN is an extremely heterogenetic glycoprotein which comprises a family of molecules which differ in their primary and secondary structures, solubilities, and by post-transcriptional alternative processing and glycosylation modifications. It exists in biological fluids as water-soluble globular dimers or as insoluble macrofibronectins in extracellular matrix fibrillar networks [42]. FN has a unique structure which allows it to change conformation from a globular to a fibrillar form [43]. Throughout conformational rearrangement, the variation in expression of the number of functional sites and glycotopes, which may be cryptic or exposed, may lead to differences in cellular activity.

Macromolecular and multidomain FN participates in physiological and pathological processes, where it has an ability to attach to cells through different binding sites. The best-known involve cell-surface receptors of the integrin type and the RGD (Arg-Gly-Asp) and RGDS (Arg-Gly-Asp-Ser) sequences of FN. Such recognition is on the basis of protein–protein interaction and leads to cell-signalling activities and signal transduction [44]. Moreover, FN can bind pathogens very effectively through the N-terminal FN fragment. Many staphylococcal and streptococcal strains can be bound in this way [39,45]. However, micro-organisms also express other types of cell-surface adhesins, bacterial lectins that are able to recognize a saccharide structure on host protein(s). FN, being a glycoprotein, may bind some pathogens through lectin-carbohydrate [39] or even carbohydrate–carbohydrate [46] interactions. Adhesion of micro-organisms to host tissues represents a critical phase in the development of many types of infection. For example, FN is important for adhesion and colonization of host tissue by Campylobacter jejuni and Campylobacter fetus which are the most frequent bacterial causes of gastrointestinal disease and diarrhoeal illness [47,48], Borrelia burgdorferi sensu lato, which causes human Lyme disease [49], and Streptococcus pneumoniae, the aetiological agent of pneumonia [45]. All of these infections are harmful during pregnancy for both mother and fetus.

Since the α(1,2)fucosylated glycans are implicated in the mediation of interactions between some pathogens and host epithelial cells, it can be postulated that the α(1,2)fucosylated FN isoform of amniotic fluid and ejaculate may play a critical role in protecting the fetus and female reproductive tract against pathogenic bacteria. Soluble fucosylated FN may act as decoy binding sites for pathogens, thus inhibiting pathogen binding to host cell ligands. Therefore the α(1,2)fucosylated glycotope of soluble FNs could constitute one of the amniotic and seminal elements of an innate immune system. On the other hand, the α(1,2)fucosylated seminal FN fragments may act as natural contraceptive agents, inhibiting human sperm–oocyte binding, since the α(1,2)fucosylated glycoconjugates are involved in the sequence of events leading to fertilization.

Concluding remarks

Currently, knowledge of the clinical value of α(1,2)fucosylated markers is limited. Studies are still in the experimental phase and require further analysis and validation. The determination of α(1,2)fucosylated glycotopes has the potential to become an additional laboratory biomarker(s) in obstetrics to monitor pregnancy and in andrology to evaluate the ejaculate of infertile men as well as in vitro fertilization. The development of new selective therapeutics on the basis of fucose-containing oligosaccharides can be considered for the future.

Glycomarkers for Disease: An Independent Meeting held at the Conference Centre of the Polish National Academy of Sciences, Wierzba, Poland, 12–16 September 2010. Organized by Sviatlana Astrautsova (Grodno, Belarus), Cathy Merry (Manchester, U.K.), Tony Merry (Manchester, U.K.), Jean-Claude Michalski (Lille, France), Grażyna Palamarczyk (Warsaw, Poland) and Krzysztof Zwierz (Białystok, Poland). Edited by Tony Merry.

Abbreviations

     
  • FN

    human fibronectin

  •  
  • IIICS

    type-III connecting segment

  •  
  • MALDI-MS

    matrix-assisted laser-desorption ionization MS

  •  
  • TOF-MS

    time-of-flight MS

  •  
  • UEA-1

    Ulex europaeus agglutinin 1

We are grateful to Dr Tony Corfield from the University of Bristol for a critical reading of the paper.

References

References
1
Carsons
S.
Lavietes
B.B.
Slomiany
A.
Diamond
H.S.
Berkowitz
E.
Carbohydrate heterogeneity of fibronectins
J. Clin. Invest.
1987
, vol. 
80
 (pg. 
1342
-
1349
)
2
Kątnik-Prastowska
I.
Kratz
M.E.
Faundez
R.
Chełmońska-Soyta
A.
Lower expression of α(2,3)- sialylated fibronectin glycoform and appearance of asialo-FN glycoform associate with high concentration of fibronectin in human seminal plasma with abnormal semen parameters
Clin. Chem. Lab. Med.
2006
, vol. 
44
 (pg. 
1119
-
1125
)
3
Hirnle
L.
Kątnik-Prastowska
I.
Amniotic fibronectin fragmentation and domain and sialyl- and fucosyl-glycotope expression associated with pregnancy complicated by intrauterine infection
Clin. Chem. Lab. Med.
2007
, vol. 
45
 (pg. 
208
-
214
)
4
Przybysz
M.
Maszczak
D.
Borysewicz
K.
Szechiński
J.
Kątnik-Prastowska
I.
Relative sialylation and fucosylation of synovial and plasma fibronectins in relation to the progression and activity of rheumatoid arthritis
Glycoconjugate J.
2007
, vol. 
24
 (pg. 
543
-
550
)
5
Tajiri
M.
Yoshida
S.
Wada
Y.
Differential analysis of site-specific glycans on plasma and cellular fibronectins: application of a hydrophilic affinity method for glycopeptide enrichment
Glycobiology
2005
, vol. 
15
 (pg. 
1332
-
1340
)
6
Ingham
K.C.
Brew
S.A.
Novokhatny
V.V.
Influence of carbohydrate on structure, stability and function of gelatin-binding fragments of fibronectin
Arch. Biochem. Biophys.
1985
, vol. 
316
 (pg. 
235
-
240
)
7
Millard
C.J.
Campbell
I.D.
Pickford
A.R.
Gelatin binding to the 8F19F1 module pair of human fibronectin requires site-specific N-glycosylation
FEBS Lett.
2005
, vol. 
579
 (pg. 
4529
-
4534
)
8
Sticht
H.
Pickford
A.R.
Potts
J.R.
Campbell
I.D.
Solution structure of the glycosylated second type 2 module of fibronectin
J. Mol. Biol.
1998
, vol. 
276
 (pg. 
177
-
187
)
9
Jones
G.E.
Arumugham
R.G.
Tanzer
M.L.
Fibronectin glycosylation modulates fibroblast adhesion and spreading
J. Cell. Biol.
1986
, vol. 
103
 (pg. 
1663
-
1670
)
10
Matsuura
H.
Greene
T.
Hakomori
S.
An α-N-acetylgalactosaminylation at the threonine residue of a defined peptide sequence creates the oncofetal peptide epitope in human fibronectin
J. Biol. Chem.
1989
, vol. 
264
 (pg. 
10472
-
10476
)
11
Tressel
T.
McCarthy
J.B.
Calaycay
J.
Le
T.D.
Legesse
K.
Shively
J.E.
Pande
H.
Human plasma fibronectin: demonstration of structural differences between the A- and B-chains in the IIICS region
Biochem. J.
1991
, vol. 
274
 (pg. 
731
-
738
)
12
Carsons
S.
Enhanced expression of a peanut agglutinin reactive O-linked oligosaccharide on fibronectins from the synovial fluid of patients with rheumatic disease, quantitation, domain localization, and functional significance
J. Rheumatol.
2002
, vol. 
29
 (pg. 
896
-
902
)
13
Köttgen
E.
Hell
B.
Müller
C.
Kainer
F.
Tauber
R.
Developmental changes in the glycosylation and binding properties of human fibronectins: characterization of glycan structures and ligand binding of human fibronectins from adult plasma, cord blood and amniotic fluid
Biol. Chem. Hoppe-Seyler
1989
, vol. 
370
 (pg. 
1285
-
1294
)
14
Leitich
H.
Egarter
C.
Kaider
A.
Hohlagschwandtner
M.
Berghammer
P.
Husslein
P.
Cervicovaginal fetal fibronectin as a marker for preterm delivery: a meta-analysis
Am. J. Obstet. Gynecol.
1998
, vol. 
180
 (pg. 
1169
-
1176
)
15
Richter
P.
Junker
K.
Franz
M.
Berndt
A.
Geyer
C.
Gajda
M.
Kosmehl
H.
Berndt
A.
Wunderlich
H.
IIICS de novo glycosylated fibronectin as a marker for invasiveness in urothelial carcinoma of the urinary bladder (UBC)
J. Cancer Res. Clin. Oncol.
2008
, vol. 
134
 (pg. 
1059
-
1065
)
16
Fukuda
M.
Levery
S.B.
Hakomori
S.
Carbohydrate structure of hamster plasma fibronectin: evidence for chemical diversity between cellular and plasma fibronectins
J. Biol. Chem.
1982
, vol. 
257
 (pg. 
6856
-
6860
)
17
Krusius
T.
Fukuda
M.
Dell
A.
Ruoslahti
E.
Structure of the carbohydrate units of human amniotic fluid fibronectin
J. Biol. Chem.
1985
, vol. 
260
 (pg. 
4110
-
4116
)
18
Takamoto
M.
Endo
T.
Isemura
M.
Kochibe
N.
Kobata
A.
Structure of asparagine-linked oligosaccharides of human placental fibronectin
J. Biochem. (Tokyo)
1989
, vol. 
105
 (pg. 
742
-
750
)
19
Reference deleted
20
Audette
G.F.
Vandonselaar
M.
Delbaere
L.T.J.
The 2.2 Å resolution structure of the O(H) blood-group-specific lectin I from Ulex europaeus
J. Mol. Biol.
2000
, vol. 
304
 (pg. 
423
-
433
)
21
Lemańska-Perek
A.
Leszek
J.
Kątnik-Prastowska
I.
Expositions of sialic acid and fucose residues on fibronectin in relation to vascular and Alzheimer's dementias. Neurobiology to Medical Practice, from Basic Sciences to Patient, Wrocław, Poland, 24 August 2010
2010
22
Hirnle
L.
Analysis of Fibronectin Molecular Forms in Amniotic Fluid and Plasma of Pregnant Women during Normal and Complicated by Intrauterine Infection Pregnancies
Habilitation Thesis
2006
Wrocław, Poland
Wrocław Medical University
23
Kątnik-Prastowska
I.
Przybysz
M.
Chełmońska-Soyta
A.
Fibronectin fragments in human seminal plasma
Acta Biochim. Pol.
2005
, vol. 
52
 (pg. 
557
-
60
)
24
Zerfaoui
M.
Fukuda
M.
Sbarra
V.
Lombardo
D.
El-Battari
A.
α(1,2)fucosylation prevents sialyl Lewis X expression and E-selectin-mediated adhesion of fucosyltransferase VII-transfected cells Eur
J. Biochem.
2000
, vol. 
267
 (pg. 
53
-
61
)
25
Chavan
M.M.
Kawle
P.D.
Mehta
N.G.
Increased sialylation and defucosylation of plasma proteins are early events in the acute phase response
Glycobiology
2005
, vol. 
15
 (pg. 
838
-
848
)
26
Becker
D.J.
Lowe
J.B.
Fucose: biosynthesis and biological function in mammals
Glycobiology
2003
, vol. 
13
 (pg. 
41R
-
53R
)
27
Li
Y.
Ma
K.
Sun
P.
Liu
S.
Qin
H.
Zhu
Z.
Wang
X.
Yan
Q.
LeY oligosaccharide upregulates DAG/PKC signaling pathway in human endometrial cells
Mol. Cell. Biochem.
2009
, vol. 
331
 (pg. 
1
-
7
)
28
Liu
J.J.
Lin
B.
Hao
Y.Y.
Li
F.-F.
Liu
D.W.
Qi
Y.
Zhu
L.C.
Zhang
S.L.
Iwamori
M.
LewisY antigen stimulates the growth of ovarian cancer cells via regulation of the epidermal growth factor receptor pathway
Oncol. Rep.
2010
, vol. 
23
 (pg. 
833
-
841
)
29
Misonou
Y.
Shida
K.
Korekane
H.
Seki
Y.
Noura
S.
Ohue
M.
Miyamoto
Y.
Comprehensive clinico-glycomic study of 16 colorectal cancer specimens: elucidation of aberrant glycosylation and its mechanistic causes in colorectal cancer cells
J. Proteome Res.
2009
, vol. 
8
 (pg. 
2990
-
3005
)
30
Issa
S.
Moran
A.P.
Ustinov
S.N.
Lin
J.H.-H.
Ligtenberg
A.J.
Karlsson
N.G.
O-linked oligosaccharides from salivary agglutinin: Helicobacter pylori binding sialyl-Lewis X and Lewis B are terminating moieties on hyperfucosylated oligo-N-acetyllactosamine
Glycobiology
2010
, vol. 
20
 (pg. 
1046
-
1057
)
31
Orczyk-Pawiłowicz
M.
Floriański
J.
Zalewski
J.
Kątnik-Prastowska
I.
Relative amounts of sialic acid and fucose of amniotic fluid glycoconjugates in relation to pregnancy age
Glycoconjugate J.
2005
, vol. 
22
 (pg. 
433
-
442
)
32
Pang
P.C.
Tissot
B.
Drobnis
E.Z.
Morris
H.R.
Dell
A.
Clark
G.F.
Analysis of the human seminal plasma glycome reveals the presence of immunomodulatory carbohydrate functional groups
J. Proteome Res.
2009
, vol. 
8
 (pg. 
4906
-
4915
)
33
Poland
D.C.
Kratz
E.
Vermeiden
J.P.
de Groot
S.M.
Bruyneel
B.
de Vries
T.
van Dijk
W.
High level of α1-acid glycoprotein in human seminal plasma is associated with high branching and expression of Lewis A groups on its glycans: supporting evidence for a prostatic origin
Prostate
2002
, vol. 
52
 (pg. 
34
-
42
)
34
Lapid
K.
Sharon
N.
Meet the multifunctional and sexy glycoforms of glycodelin
Glycobiology
2006
, vol. 
16
 (pg. 
39R
-
45R
)
35
Chaturvedi
P.
Warren
C.D.
Altaye
M.
Morrow
A.L.
Ruiz-Palacios
G.
Pickering
L.K.
Newburg
D.S.
Fucosylated human-milk oligosaccharides vary between individuals and over the course of lactation
Glycobiology
2001
, vol. 
11
 (pg. 
365
-
372
)
36
Ge
C.H.
Kong
Y.
Wang
H.
Zhu
Z.M.
Effects of blastocyst surface oligosaccharide LeY on secretion and expression of matrix metalloproteinase in vivo
Acta Biochim. Biophys. Sin.
2002
, vol. 
34
 (pg. 
45
-
49
)
37
Kulovidouris
S.A.
Gama
C.I.
Lee
L.W.
Hsieh-Wilson
L.C.
A role for fucose α(1–2) galactose carbohydrates in neuronal growth
J. Am. Chem. Soc.
2005
, vol. 
127
 (pg. 
1340
-
1341
)
38
Murrey
H.E.
Ficarro
S.B.
Krishnamurthy
C.
Domino
S.E.
Peters
E.C.
Hsieh-Wilson
L.C.
Identification of the plasticity-relevant fucose-α(1–2) galactose proteome from the mouse olfactory bulb
Biochemistry
2009
, vol. 
48
 (pg. 
7261
-
7270
)
39
Hooper
L.V.
Gordon
J.I.
Glycans as legislators of host–microbial interactions: spanning the spectrum from symbiosis to pathogenicity
Glycobiology
2001
, vol. 
11
 (pg. 
1R
-
10R
)
40
Domino
S.E.
Hurd
E.A.
Thomsson
K.A.
Karnak
D.M.
Holmén Larsson
J.M.
Thomsson
E.
Bäckström
M.
Hansson
G.C.
Cervical mucins carry α(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis
Glycoconjugate J.
2009
, vol. 
26
 (pg. 
1125
-
1134
)
41
Newburg
D.S.
Ruiz-Palacios
G.M.
Morrow
A.L.
Human-milk glycans protect infants against enteric pathogens
Annu. Rev. Nutr.
2005
, vol. 
25
 (pg. 
37
-
58
)
42
Mao
Y.
Schwarzbauer
J.E.
Fibronectin fibrillogenesis, a cell-mediated matrix assembly process
Matrix Biol.
2005
, vol. 
24
 (pg. 
389
-
399
)
43
Vakonakis
I.
Staunton
D.
Ellis
I.R.
Sarkies
P.
Flanagan
A.
Schor
A.M.
Seth
L.
Schor
S.L.
Campbell
I.D.
Motogenic sites in human fibronectin are masked by long range interactions
J. Biol. Chem.
2009
, vol. 
284
 (pg. 
15668
-
15675
)
44
Pankov
R.
Yamada
K.M.
Fibronectin at a glance
J. Cell Sci.
2002
, vol. 
115
 (pg. 
3861
-
3863
)
45
Papasergi
S.
Garibaldi
M.
Tuscano
G.
Signorino
G.
Ricci
S.
Peppoloni
S.
Pernice
I.
Lo Passo
C.
Teti
G.
Felici
F.
Beninati
C.
Plasminogen- and fibronectin-binding protein B is involved in the adherence of Streptococcus pneumoniae to human epithelial cells
J. Biol. Chem.
2010
, vol. 
285
 (pg. 
7517
-
7524
)
46
Zheng
M.
Hakomori
S.I.
Soluble fibronectin interaction with cell surface and extracellular matrix is mediated by carbohydrate to-carbohydrate interaction
Arch. Biochem. Biophys.
2000
, vol. 
374
 (pg. 
93
-
99
)
47
Konkel
M.E.
Larson
C.L.
Flanagan
R.C.
Campylobacter jeluni FlpA binds fibronectin and is required for maximal host cell adherence
J. Bacteriol.
2010
, vol. 
192
 (pg. 
68
-
76
)
48
Graham
L.L.
Friel
T.
Woodman
R.L.
Fibronectin enhances Campylobacter fetus interaction with extracellular matrix components and INT 407 cells
Can J. Microbiol.
2008
, vol. 
54
 (pg. 
37
-
47
)
49
Brissette
C.A.
Rossmann
E.
Bowman
A.
Cooley
A.E.
Riley
S.P.
Hunfeld
K.-P.
Bechtel
M.
Kraiczy
P.
Stevenson
B.
The Borrelial fibronectin-binding protein RevA is an early antigen of human Lyme disease. Clin
Vaccine Immunol.
2010
, vol. 
17
 (pg. 
274
-
280
)