Toshisuke Kawasaki

Ritsumeikan University, Kioto, Kyōto, Japan

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Publications (210)616.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We have generated a mouse monoclonal antibody (R-17F, IgG1 subtype) specific to human induced pluripotent stem (hiPS)/embryonic stem (ES) cells by using a hiPS cell line as an antigen. Triple-color confocal immunostaining images of hiPS cells with R-17F indicated that the R-17F epitope was expressed exclusively and intensively on the cell membranes of hiPS cells, and co-localized partially with those of SSEA-4 and SSEA-3. Lines of evidence suggested that the predominant part of the R-17F epitope was a glycolipid. Upon TLC blot of total lipid extracts from hiPS cells with R-17F, one major R-17F positive band was observed at a slow migration position close to that of anti-blood group H1(O) antigen. MALDI-TOF-MS and MSn analyses of the purified antigen indicated that the presumptive structure of the R-17F antigen was Fuc-Hex-HexNAc-Hex-Hex-Cer. Glycan microarray analysis involving 13 different synthetic oligosaccharides indicated that R-17F bound selectively to LNFP I (Fucα1-2Galβ1-3GlcNAcβ1-3Galβ1-4Glc). A critical role of the terminal Fucα1-2 residue was confirmed by the selective disappearance of R-17F binding to the purified antigen on α1-2 fucosidase digestion. Most interestingly, R-17F, when added to hiPS/ES cell suspensions, exhibited potent dose-dependent cytotoxicity. The cytotoxic effect was augmented markedly on addition of the secondary antibody (goat anti-mouse IgG1 antibody). R-17F may be beneficial for safer regenerative medicine by eliminating residual undifferentiated hiPS cells in hiPS-derived regenerative tissues, which are considered to be a strong risk factor for carcinogenesis. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 06/2015; 290(33). DOI:10.1074/jbc.M115.657692 · 4.57 Impact Factor
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    ABSTRACT: Induced pluripotent stem cells (iPSCs) offer an invaluable tool for biological research and regenerative medicine. We report establishment of rat iPSCs (riPSCs) using a plasmid vector encoding four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. Although all riPSC clones were generated and cultured under the same conditions, expressed hallmark pluripotency markers and differentiated successfully in vitro, the expression of a keratan sulfate glycan epitope with unique properties defined by R-10G antibody varied in the riPSC clones. In contrast, tumor rejection antigen (TRA)-1-81 epitope expression was comparable. A clone highly reactive to R-10G antibody formed teratomas in vivo consisting of cells from all three germ layers. However, clones expressing a lower level of the epitope defined by R-10G resulted in tumors with rapid growth consisting of undifferentiated cells. Additionally, riPSCs could be successfully differentiated into a neuronal lineage including glutamate neurons that responded to agonist stimulation. These observations demonstrate a glyco-phenotypic difference that may potentially serve as a useful probe for riPSC evaluation and to study the role of glycans in pluri potency and carcinogenesis in these cells.
    Biological & Pharmaceutical Bulletin 05/2015; 38(38):127-133. DOI:10.1248/bpb.b14-00697 · 1.83 Impact Factor
  • Toshisuke Kawasaki ·

    Glycoconjugate Journal 11/2014; 31(8):545-6. DOI:10.1007/s10719-014-9552-8 · 2.52 Impact Factor
  • Motohiro Nonaka · Toshisuke Kawasaki ·
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    ABSTRACT: Function of lectin depends on its amino acid sequence of carbohydrate-recognition domain (CRD), conformation, and extracellular/intracellular localization. Altering lectin gene expression by over-expression or knockdown is a powerful tool for analyzing its cellular function. Here, we describe a method of lectin gene over-expression, taking a C-type lectin, mannan-binding protein (MBP), as an example. Carbohydrate-binding ability of MBP, its subcellular localization, and functional co-localization with ligand glycoprotein are assayed comparing with an inactive mutant MBP.
    Methods in Molecular Biology 08/2014; 1200:389-99. DOI:10.1007/978-1-4939-1292-6_34 · 1.29 Impact Factor
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    ABSTRACT: Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200-600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolated from human colorectal carcinoma (SW1116) cells and characterized as highly fucosylated high m.w. type 1 Lewis glycans. In this study, we first demonstrated that MBP recognizes human primary colorectal carcinoma tissues through tumor-associated MBP ligands. We performed fluorescence-based histochemistry of MBP in human colorectal carcinoma tissues and showed that MBP clearly stained cancer mucosae in a Ca(2+)-dependent manner. Coincubation with plant (Aleuria aurantia) lectin, but not Con A, blocked MBP staining, indicating that fucose, rather than mannose, is involved in this interaction. The expression of MBP ligands was detected in 127 of 330 patients (38.5%), whereas, most significantly, there was no expression in 69 nonmalignant tissues. The MBP-staining pattern in cancer mucosae significantly overlapped with that of Lewis b [Fucα1-2Galβ1-3(Fucα1-4)GlcNAc] staining, but the Lewis b staining in normal tissues was not associated with MBP staining. In addition, the MBP staining correlated inversely with the expression of CA19-9 Ag, and MBP stained 11 of 25 (44%) CA19-9 (sialyl Lewis a [NeuAc(α2-3)Galβ1-3(Fucα1-4)GlcNAc])(-) colorectal carcinoma tissues. We found a favorable prognosis in patients with MBP ligand(+) tumors. These results suggest that selective recognition of cancer cells by endogenous MBP seems to be associated with an antitumor effect and that tissue staining with MBP in combination with CA19-9 may serve as a novel indicator of colorectal carcinoma tissues.
    The Journal of Immunology 01/2014; 192(3). DOI:10.4049/jimmunol.1203023 · 4.92 Impact Factor
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    ABSTRACT: We have generated a monoclonal antibody (R-10G) specific to human induced pluripotent stem (hiPS)/embryonic stem (hES) cells by using hiPS cells (Tic) as an antigen, followed by differential screening of mouse hybridomas with hiPS and human embryonal carcinoma (hEC) cells. Upon Western blotting with R-10G, human iPS/ES cell lysates gave a single but an unusually diffuse band at a position corresponding to over 250 kDa. The antigen protein was isolated from the iPS cell lysates with an affinity column of R-10G. The R-10G positive band was resistant to digestion with PNGase F, neuraminidase, fucosidase, chondrotinase ABC, and heparinase mix, but it disappeared almost completely on digestion with keratanase, keratanase II, and endo-β-galactosidase, indicating that the R-10G epitope is a keratan sulfate. The carrier protein of the R-10G epitope was identified as podocalyxin by LC/MS/MS analysis of the R-10G positive-protein band material obtained on SDS-PAGE. The R-10G epitope is a type of keratan sulfate with some unique properties. (1) The epitope is expressed only on hiPS/ES cells, i.e., not on hEC cells, unlike those recognized by the conventional hiPS/ES marker antibodies. (2) The epitope is a type of keratan sulfate lacking oversulfated structures and is not immunologically cross-reactive with high sulfated-keratan sulfate. (3) The R-10G epitope is distributed heterogeneously on hiPS cells, suggesting that a single colony of undifferentiated hiPS cells consists of different cell subtypes. Thus, R-10G is a novel antibody recognizing hiPS/ES cells, and should be a new molecular probe for disclosing the roles of glycans on these cells.
    Glycobiology 11/2012; 23(3). DOI:10.1093/glycob/cws159 · 3.15 Impact Factor
  • Makoto Hirano · Bruce Y Ma · Nobuko Kawasaki · Shogo Oka · Toshisuke Kawasaki ·
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    ABSTRACT: Ischemia/reperfusion (I/R) is an important cause of acute renal failure. Recent studies have shown that the complement system mediated by the mannan-binding protein (MBP), which is a C-type serum lectin recognizing mannose, fucose and N-acetylglucosamine residues, plays a critical role in the pathogenesis of ischemic acute renal failure. MBP causes complement activation through the MBP lectin pathway and a resulting complement component, C3b, is accumulated on the brush borders of kidney proximal tubules in a renal I/R-operated mouse kidney. However, the initial step of the complement activation has not been studied extensively. We previously identified both meprins α and β, highly glycosylated zinc metalloproteases, localized on kidney proximal tubules as endogenous MBP ligands. In the present study, we demonstrated that serum-type MBP (S-MBP) and C3b were co-localized with meprins on both the cortex and the medulla in the renal I/R-operated mouse kidney. S-MBP was indicated to interact with meprins in vivo in the I/R-operated mouse kidney and was shown to initiate the complement activation through the interaction with meprins in vitro. Taken together, the present study strongly suggested that the binding of S-MBP to meprins triggers the complement activation through the lectin pathway and may cause the acute renal failure due to I/R on kidney transplantation and hemorrhagic shock.
    Glycobiology 08/2011; 22(1):84-95. DOI:10.1093/glycob/cwr107 · 3.15 Impact Factor
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    ABSTRACT: Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA.
    Journal of Biological Chemistry 06/2011; 286(25):22403-13. DOI:10.1074/jbc.M110.215301 · 4.57 Impact Factor
  • Nobuko Kawasaki · Toshisuke Kawasaki ·
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    ABSTRACT: Animal lectins have contributed greatly to understanding of the physiological significance of glycans in man and animals. Mannan-binding protein (MBP) binds to mannose, N-acetylglucosamine and L-fucose via the carbohydrate binding sites in its carbohydrate recognition domain (CRD). In pathogenic microorganisms, manno-oligosaccharides on the cell surface appear to be the major glycans involved in the interaction with MBP, whereas in human colorectal carcinoma SW1116 cells, which are endogenous target cells of MBP, Lewis (Le)-type oligosaccharides with the type I structure appear to play a major role in the interaction with the lectin. In fact, MBP ligand oligosaccharides (MLO), which have complex type N-glycans with at least 4 Fuc(Hex-HexNAc) units, have been isolated with an MBP affinity column, whereas complex type N-glycans having 3 or less Fuc(Hex-HexNAc) units as well as high-mannose type structures (Man5 to Man8) did not bind to the MBP affinity column. The structures of MLO are very unique and distinct from those of other previously reported tumor-specific carbohydrate antigens, and thus should be considered as representative of a new family of tumor-associated carbohydrate antigens. The reasons why and how MLO exhibits such strong affinity to MBP are not clear at present but computer modeling suggested the possibility that a MBP-Lewis oligosaccharides complex may be formed between the trimeric structure of the carbohydrate recognition domain (CRD) and Leb-(Lea)x4-Lex, a typical example of the nonreducing terminal oligosaccharide structure of MLO.
    Trends in Glycoscience and Glycotechnology 01/2010; 22(125):141-151. DOI:10.4052/tigg.22.141 · 0.41 Impact Factor
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    Ippei Morita · Shinako Kakuda · Yusuke Takeuchi · Toshisuke Kawasaki · Shogo Oka ·
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    ABSTRACT: The human natural killer-1 (HNK-1) glyco-epitope possesses a unique structural feature, a sulfated glucuronic acid attached to lactosamine on the non-reducing termini of glycans. The expression of HNK-1 is temporally and spatially regulated by glucuronyltransferase (GlcAT-P) in the brain. Our previous report showed that mice lacking GlcAT-P almost completely lost HNK-1 expression in the brain and exhibited reduced long-term potentiation (LTP) at hippocampal CA1 synapses. GlcAT-P-deficient mice also showed impaired hippocampus-dependent spatial learning. Although HNK-1 plays an essential role in synaptic plasticity and memory formation, it remains unclear how HNK-1 regulates these functions. In this study, we showed that loss of the HNK-1 epitope resulted in an increase of filopodium-like immature spines and a decrease of mushroom-like mature spines in both the early postnatal mouse hippocampus and cultured hippocampal neurons. However, HNK-1 had no influence on spine density or filopodium formation. Immunofluorescence staining revealed that loss of HNK-1 altered the distribution of postsynaptic proteins such as α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-type glutamate receptor subunit GluR2 and PSD-95 from spine heads onto dendritic shafts without affecting synapse formation, resulting in an increase of shaft synapses in cultured GlcAT-P-deficient neurons. GluR2, a major HNK-1 carrier glycoprotein in postsynaptic density, has the ability to promote spine morphogenesis. Overexpression of GluR2 promoted spine growth in both wild-type and GlcAT-P-deficient neurons, but the increase in GlcAT-P-deficient neurons was lower than that in wild-type neurons. This is the first evidence that HNK-1 is a key factor for normal dendritic spine maturation and is involved in the distribution of postsynaptic proteins.
    Neuroscience 12/2009; 164(4). DOI:10.1016/j.neuroscience.2009.09.065 · 3.36 Impact Factor
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    ABSTRACT: HNK-1 (human natural killer-1) glyco-epitope, a sulfated glucuronic acid attached to N-acetyllactosamine on the nonreducing termini of glycans, is highly expressed in the nervous system. Our previous report showed that mice lacking a glucuronyltransferase (GlcAT-P), a key enzyme for biosynthesis of the HNK-1 epitope, showed reduced long term potentiation at hippocampal CA1 synapses. In this study, we identified an α-amino-3-hydroxy-5-methylisoxazole propionate (AMPA)-type glutamate receptor subunit, GluR2, which directly contributes to excitatory synaptic transmission and synaptic plasticity, as a novel HNK-1 carrier molecule. We demonstrated that the HNK-1 epitope is specifically expressed on the N-linked glycan(s) on GluR2 among the glutamate receptors tested, and the glycan structure, including HNK-1 on GluR2, was determined using liquid chromatography-tandem mass spectrometry. As for the function of HNK-1 on GluR2, we found that the GluR2 not carrying HNK-1 was dramatically endocytosed and expressed less on the cell surface compared with GluR2 carrying HNK-1 in both cultured hippocampal neurons and heterologous cells. These results suggest that HNK-1 stabilizes GluR2 on neuronal surface membranes and regulates the number of surface AMPA receptors. Moreover, we showed that the expression of the HNK-1 epitope enhanced the interaction between GluR2 and N-cadherin, which has important roles in AMPA receptor trafficking. Our findings suggest that the HNK-1 epitope on GluR2 regulates cell surface stability of GluR2 by modulating the interaction with N-cadherin.
    Journal of Biological Chemistry 10/2009; 284(44):30209-17. DOI:10.1074/jbc.M109.024208 · 4.57 Impact Factor
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    ABSTRACT: Serum MBP, also known as MBL, is a C-type lectin that is known to be a soluble host defense factor involved in innate immunity. It has been well established that dying microbes and apoptotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display fragmented DNA on their surfaces. However, PRRs that mediate the recognition and clearance of free DNA and fragmented DNA in apoptotic cells have not been characterized clearly. Although MBP was reported recently to bind DNA as a novel ligand, binding characterization and the recognition implications have not been addressed yet. In this study, we show that MBP can bind DNA and RNA in a calcium-dependent manner from a variety of origins, including bacteria, plasmids, synthetic oligonucleotides, and fragmented DNA of apoptotic cells. Direct binding and competition studies indicate that MBP binds nucleic acids via its CRD to varying degrees and that MBP binds dsDNA more effectively than ssDNA and ssRNA. Furthermore, we reveal that the MBP-DNA complex does not trigger complement activation via the MBP lectin pathway, and the lectin pathway of complement activation is required for MBP-mediated enhancement of phagocytosis of targets bearing MBP ligands and that MBP can recognize the fragmented DNA presented on apoptotic cells. Therefore, we propose that the MBP lectin pathway may support effective recognition and clearance of cellular debris by facilitating phagocytosis, possibly through immunomodulatory mechanisms, thus preventing autoimmunity.
    Journal of leukocyte biology 06/2009; 86(3):737-48. DOI:10.1189/jlb.1008674 · 4.29 Impact Factor
  • Daisuke Anzai · Yasuhiro Tonoyama · Atsushi Ikeda · Toshisuke Kawasaki · Shogo Oka ·
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    ABSTRACT: Carbohydrates are known to play essential roles in various biological processes including development. However, it remains largely unknown which carbohydrate structure takes part in each biological event. Here, we examined the roles of the human natural killer-1 (HNK-1) carbohydrate in medaka embryogenesis. We first cloned two medaka glucuronyltransferases, GlcAT-P and GlcAT-S, key enzymes for HNK-1 biosynthesis. Overexpression of these glucuronyltransferases affected morphogenetic processes. In addition, loss-of-function experiments revealed that GlcAT-P is physiologically indispensable for head morphogenesis and GlcAT-P depletion also led to markedly increased apoptosis. However, even when the apoptosis was blocked, abnormal head morphogenesis caused by GlcAT-P depletion was still observed, indicating that apoptosis was not the main cause of the abnormality. Moreover, in situ hybridization analyses indicated that GlcAT-P depletion resulted in the abnormal formation of the nervous system but not in cell specification. These results suggest that tight regulation of HNK-1 expression is essential for proper morphogenesis of medaka embryos.
    Glycobiology 05/2009; 19(8):868-78. DOI:10.1093/glycob/cwp060 · 3.15 Impact Factor
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    ABSTRACT: Glycans are known to play important roles in vertebrate development; however, it is difficult to analyze in mammals because it takes place in utero. Therefore, we used medaka (Oryzias latipes) to clarify the roles of glycans during vertebrate development. beta-1,4-Galactosyltransferase is one of the key enzymes in the biosynthesis of the lactosamine structures that are commonly found on glycoproteins and glycolipids. Here, we show the essential role of beta4GalT2 during medaka development. Depletion of beta4GalT2 by morpholino antisense oligonucleotide injection resulted in significant morphological defects, such as shortening of the anterior-posterior axis, cyclopia, impaired somite segmentation, and head hypoplasia. In situ hybridization analyses revealed that the loss of beta4GalT2 led to defective anterior-posterior axis elongation during gastrulation without affecting organizer formation. Furthermore, a cell tracing experiment demonstrated that beta4GalT2 knockdown mainly affects mediolateral cell intercalation, which contributes to anterior-posterior axis elongation. A cell transplantation experiment indicated that glycans are produced by beta4GalT2 cell-autonomously during gastrulation. beta4GalT2 depletion also led to enhanced apoptosis; however, this does not account for the phenotypic abnormalities, as blockade of apoptosis failed to compensate for the beta4GalT2 depletion. Our data suggest that beta4GalT2 activity is cell-autonomously required in cells undergoing mediolateral cell intercalation, which drives extension movements during medaka gastrulation.
    Mechanisms of development 04/2009; 126(7):580-94. DOI:10.1016/j.mod.2009.03.004 · 2.44 Impact Factor
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    ABSTRACT: The serum mannan-binding protein (MBP) is a host defense C-type lectin specific for mannose, N-acetylglucosamine, and fucose residues, and exhibits growth inhibitory activity toward human colorectal carcinoma cells. The MBP-ligand oligosaccharides (MLO) isolated from a human colorectal carcinoma cell line, SW1116, are large, multiantennary N-glycans with highly fucosylated polylactosamine-type structures having Le(b)-Le(a) or tandem repeats of the Le(a) structure at their nonreducing ends. In this study, we isolated the major MBP-ligand glycoproteins from SW1116 cell lysates with an MBP column and identified them as CD26/dipeptidyl peptidase IV (DPPIV) (110 kDa) and CD98 heavy chain (CD98hc)/4F2hc (82 kDa). Glycosidase digestion revealed that CD26 contained such complex-type N-glycans that appear to mediate the MBP binding. MALDI-MS of the N-glycans released from CD26 by PNGase F demonstrated conclusively that CD26 is the major MLO-carrying protein. More interestingly, a comparison of the N-glycans released from the MBP-binding and non-MBP-binding glycopeptides suggested that complex-type N-glycans carrying a minimum of 4 Le(a)/Le(b) epitopes arranged either as multimeric tandem repeats or terminal epitopes on multiantennary structures are critically important for the high affinity binding to MBP. Analysis of the N-glycan attachment sites demonstrated that the high affinity MLO was expressed preferentially at some N-glycosylation sites, but this site preference was not so stringent. Finally, hypothetical 3D models of tandem repeats of the Le(a) epitope and the MBP-Lewis oligosaccharide complex were presented.
    Glycobiology 02/2009; 19(4):437-50. DOI:10.1093/glycob/cwn158 · 3.15 Impact Factor
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    ABSTRACT: It has been well established that CD45 is a key receptor-type protein tyrosine phosphatase (PTPase) regulating Src-family protein tyrosine kinase (Src-PTK) in T and B lymphocytes. However, precisely how CD45 exerts its effect in these lymphocytes remains controversial. We recently reported that Jacalin, an alpha-O-glycoside of the disaccharide Thomsen-Friedenreich antigen-specific lectin from jackfruit seeds, caused marked T-cell activation in response to T-cell receptor ligation and CD28 costimulation by binding to CD45. On extending the reported research, we found that CD45 and isoforms are major Jacalin receptors on B lymphocytes, and that the glycosylation of CD45 is involved in the interaction of Jacalin with the PTPase. In contrast to Jacalin-stimulated T-cell activation, we found that Jacalin induced human B-lymphocyte apoptosis, resulting in calcium mobilization and calpain activation, suggesting that the calcium-calpain pathway may mediate the Jacalin-induced apoptosis. Importantly, the apoptosis was effectively blocked by a specific CD45 PTPase inhibitor, indicating that Jacalin induces human B-lymphocyte apoptosis through CD45 triggering. Furthermore, we found that Jacalin significantly increased the C-terminal inhibitory tyrosine (Tyr507) phosphorylation of Src-PTK Lyn, one of the major substrates of CD45 PTPase, and this effect was also observed on incubation of B lymphocytes with the specific CD45 PTPase inhibitor, suggesting that Jacalin stimulation results in increasing C-terminal tyrosine phosphorylation of the kinase through inhibition of CD45 tyrosine phosphatase activity in human B lymphocytes. Therefore, the down-modulation of Lyn kinase may play a role in the regulation of B-lymphocyte viability.
    Immunology 11/2008; 127(4):477-88. DOI:10.1111/j.1365-2567.2008.02977.x · 3.80 Impact Factor
  • Mothiro Nonaka · Bruce Yong Ma · Toshisuke Kawasaki ·

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 09/2008; 53(12 Suppl):1649-54.
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    Open Glycoscience 06/2008; 1(1):8-18. DOI:10.2174/1875398100801010008
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    ABSTRACT: Dendritic cells (DCs) are APCs that play an essential role by bridging innate and adaptive immunity. DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is one of the major C-type lectins expressed on DCs and exhibits high affinity for nonsialylated Lewis (Le) glycans. Recently, we reported the characterization of oligosaccharide ligands expressed on SW1116, a typical human colorectal carcinoma recognized by mannan-binding protein, which is a serum C-type lectin and has similar carbohydrate-recognition specificities as DC-SIGN. These tumor-specific oligosaccharide ligands were shown to comprise clusters of tandem repeats of Lea/Leb epitopes. In this study, we show that DC-SIGN is involved in the interaction of DCs with SW1116 cells through the recognition of aberrantly glycosylated forms of Lea/Leb glycans on carcinoembryonic Ag (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1). DC-SIGN ligands containing Lea/Leb glycans are also highly expressed on primary cancer colon epithelia but not on normal colon epithelia, and DC-SIGN is suggested to be involved in the association between DCs and colorectal cancer cells in situ by DC-SIGN recognizing these cancer-related Le glycan ligands. Furthermore, when monocyte-derived DCs (MoDCs) were cocultured with SW1116 cells, LPS-induced immunosuppressive cytokines such as IL-6 and IL-10 were increased. The effects were significantly suppressed by blocking Abs against DC-SIGN. Strikingly, LPS-induced MoDC maturation was inhibited by supernatants of cocultures with SW1116 cells. Our findings imply that colorectal carcinomas affecting DC function and differentiation through interactions between DC-SIGN and colorectal tumor-associated Le glycans may induce generalized failure of a host to mount an effective antitumor response.
    The Journal of Immunology 04/2008; 180(5):3347-56. DOI:10.4049/jimmunol.180.5.3347 · 4.92 Impact Factor
  • Nobuko Kawasaki · Bruce Yong Ma · Toshisuke Kawasaki ·
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    ABSTRACT: Mannan-binding protein (MBP), also called mannose-binding protein (MBP) or mannanbinding lectin (MBL), is a Ca2+-dependent (C-type) mammalian lectin specific for mannose, N-acetylglucosamine (GlcNAc), and fucose, and is an important serum component associated with innate immunity. Human MBP is a homooligomer of an approximately 31 kDa subunit, each subunit containing a carbohydrate recognition domain (CRD) followed by a short neck region on the COOH terminal side and a collagen-like domain followed by a short cysteine-rich region on the NH2 terminal side. Three subunits form a structural unit, and MBP normally consists of 3–6 structural units joined through disulfide bonds at the NH2 termini, the whole molecular mass being approximately 300–600 kDa. MBP is a pattern-recognition molecule of the innate immune system that promotes phagocytosis of microorganisms through “the lectin pathway” of complement activation when it binds to ligand sugars such as mannose and GlcNAc on microbes (Kawasaki 1999) (see Fig. 1). More recently, MBP was found to have potent growth inhibitory activity to human colorectal carcinoma cell line, SW1116, in vivo via a complement- independent mechanism (Ma et al. 1999). This was proposed to term MBP-dependent cell-mediated cytotoxicity (MDCC). The MBP-ligand oligosaccharides expressed on the surface of SW1116 cells, which were assumed to be associated with MDCC, were isolated and characterized (Terada et al. 2005). Endogenous ligands for MBP were shown to be expressed highly in the brush border epithelial cells of kidney proximal tubules, and both meprin α and β have been identified as novel endogen MBP ligand proteins.
    12/2007: pages 162-166;

Publication Stats

6k Citations
616.67 Total Impact Points


  • 2005-2015
    • Ritsumeikan University
      • Research Center for Glycobiotechnology
      Kioto, Kyōto, Japan
    • Juntendo University
      Edo, Tōkyō, Japan
  • 1969-2007
    • Kyoto University
      • • Division of Pharmaceutical Sciences
      • • Department of Synthetic Chemistry and Biological Chemistry
      Kioto, Kyōto, Japan
  • 1998
    • Kyoto Pharmaceutical University
      Kioto, Kyōto, Japan
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 1997
    • University of Hamburg
      • Center for Molecular Neurobiology (ZMNH)
      Hamburg, Hamburg, Germany
  • 1995
    • Kobe Pharmaceutical University
      Kōbe, Hyōgo, Japan
  • 1988-1993
    • Kyoto Sangyo University
      • Department of Molecular Biosciences
      Kioto, Kyōto, Japan
  • 1989
    • Universiteit Utrecht
      • Division of Organic Chemistry and Catalysis
      Utrecht, Provincie Utrecht, Netherlands
  • 1983
    • Kansai Medical University
      • Department of Physiology
      Moriguchi, Ōsaka, Japan