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M Kiso

Publications and source records attributed to M Kiso.

At least 73 records · Page 4Linked to original sources
PubMed1996

Two different sialidases, KDN-sialidase and regular sialidase in the starfish Asterina pectinifera.

We have found the coexistence of two different sialidases in the entrails of the starfish Asterina pectinifera: a regular sialidase (RS), which cleaves sialic acid from sialoglycoconjugates, and a KDN-sialidase (KS) which releases the sialic acid analogue KDN (2-keto-3-deoxy-D-glycero-d-galacto-nononic acid) from KDN-containing glycoconjugates that are resistant to RS. The 6700-fold purified KS and 1300-fold purified RS were prepared to study the properties of these two sialidases. KS and RS from Asterina starfish differ in several properties other than glycon specificity, including molecular mass, isoelectric point (pI) and susceptibility to competitive and non-competitive inhibitors. KS has a molecular mass of 31 kDa and a pI of 8.3 while RS has a molecular mass of 128 kDa and a pI of about 4.8. 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (NeuAc2en), but not 2,3-dehydro-2-deoxy-KDN (KDN2en), is a potent competitive inhibitor of RS (Ki approximately 0.007 mM); however, both NeuAc2en and KDN2en are moderate inhibitors of KS (K1 approximately 0.04 mM). Hg2+ is a potent non-competitive inhibitor of RS but not of KS. KS and RS were examined for their ability to hydrolyse KDN- and NeuAc-containing glycoconjugates. KS hydrolyses 4-methyl-umbelliferyl-alpha-KDN (MU-KDN) 20 times faster than 4-methylumbelliferyl-alpha-NeuAc (MU-NeuAc), while RS hydrolyses MU-NeuAc 88 times faster than MU-KDN at the pH optimum of 4.0 KS effectively hydrolyses KDN-GM3 (where GM3 is NeuAc alpha 2 --> 3Gal beta 1 --> 4Glc beta 1-1' Cer, and Cer is ceramide), KDN alpha 2 --> 3lactose, KDN alpha 2 --> 6lactose, KDN alpha 2 --> 6N-acetylgalactosaminitol, KDN alpha 2 --> 6 (KDN alpha 2 --> 3)N-acetylgalactosaminitol and KDN alpha 2 --> 6(GlcNAc beta 1 --> 3) N-acetylgalactosaminitol. However, under the same conditions, these KDN-containing glycoconjugates are refractory to RS. Conversely, GM3, NeuAc alpha 2 --> 3lactose and NeuAc alpha 2 --> 6lactose are effectively hydrolysed by RS but not by KS.

Animals↗
PubMed1996

Systematic synthesis of alpha-sialyl-(2 --> 3)- and -(2 --> 6)-isoglobopentaosylceramides (V3Neu5AciGb5Cer and V6Neu5AciGb5Cer).

Systematic syntheses of the isoglobo-series gangliosides, alpha-sialyl-(2 --> 3)- and -(2 --> 6)-isoglobopentaosyl ceramides (21 and 24, V3Neu5AciGb5Cer and V6Neu5AciGb5Cer) are described. 2-(Trimethylsilyl)ethyl 2-O-benzyl-4,6-O-benzylidene-alpha-D-galactopyranosyl-(1 --> 3)- 2,4,6,tri-O-benzyl-beta-D-galactopyranosyl-(1--> 4) -2,3,6-tri-O-benzyl-bet a-D- glucopyranoside (4), the core structure of the isoglobo-series gangliosides was prepared by the glycosylation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-(1 --> 4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (2) with methyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-1-thio-beta-D-galactopyranoside (1), and subsequent O-deacetylation. Coupling of 4 and methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-beta-D- galactopyranoside gave an isoglobotetraoside derivative 6, from which the phthaloyl and O-acetyl groups were removed. N-Acetylation then gave a tetrasaccharide acceptor 7. Dimethyl(methylthio)sulfonium triflate-promoted coupling of 7 with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D- galacto)-(2 --> 3)-2,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyranoside or -(2 --> 6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-beta-D-galactopyranoside gave the pentasaccharide derivative 9 and 14 in good yields. Compounds 9 and 14 were converted into the corresponding alpha-trichloroimidates 12 and 17 which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18), gave the beta-glycoside 19 and 22 respectively, Finally, 19 and 22 were transformed, via selective reduction of azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group into 21 and 24, respectively.

Acetylation↗
PubMed1996

Functional role of sialyl Lewis X and fibronectin-derived RGDS peptide analogue on tumor-cell arrest in lungs followed by extravasation.

Our study demonstrates that synthetic sialyl Lewis X (SLex) as a ligand for selectins and fibronectin-derived RGDS peptide analogue [Ar(DRGDS)3] inhibits lung metastases produced by i.v. co-injection of B16-BL6 melanoma cells. To investigate the inhibitory mechanisms in a living animal, we performed positron-emission tomography (PET) analysis after i.v. injection of [2-18F]2-fluoro-2v-deoxy-D-glucose-labeled tumor cells with or without liposomal SLex or Ar(DRGDS)3. The real-time PET measurement for the first 120 min, started immediately after injection, showed that tumor-cell arrest, i.e., accumulation in the target organ (lung) was remarkably inhibited by liposomal SLex, but not inhibited by Ar(DRGDS)3 or liposomal Me-SLex, which is not recognized by selectins. In contrast, Ar(DRGDS)3 inhibited the invasion of B16-BL6 cells into reconstituted basement membrane (Matrigel) following tumor arrest, whereas SLex- or Me-SLex-entrapped liposomes did not affect tumor invasion. In the metastatic processes containing tumor-cell lodgement and arrest in the target organ followed by extravasation (invasion), SLex resulted in the inhibition of initial arrest of tumor cells, presumably tumor-endothelium interaction, while Ar(DRGDS)3 achieved inhibition of tumor invasion into basement membrane at later steps of the cascade, consequently leading to inhibition of metastasis. Thus, tumor-cell arrest in lungs in the metastatic processes must be precisely and properly controlled by different adhesion molecules at different stages, which are similar to those observed in leukocyte-endothelium interaction.

Amino Acid Sequence↗
PubMed1996

Studies on selectin blocker. 1. Structure-activity relationships of sialyl Lewis X analogs.

As part of our studies of selectin blockers, we prepared 1-deoxy-3'-O-sulfo LeX analogs (1-3), 1-deoxy-3'-O-phosphono LeX analogs (4), and 1-deoxy sLeX analogs (5-7), and examined their inhibitory activities against natural ligand (sLeX) binding to E-selectin, P-selectin, and L-selectin. The 1-deoxy sLeX 5 was up to 20 times more potent an inhibitor than the sLeX tetrasaccharide toward P- and L-selectin binding. This indicates that the modification of the 1 or 2 position of sLeX is useful in the design of a more potent selectin blocker.

E-Selectin↗
PubMed1996

Total synthesis of VIM-2 ganglioside isolated from human chronic myelogenous leukemia cells.

A total synthesis of the tumor-associated glycolipid antigen, VIM-2, is described [2]. Phenyl 2,3,4-tri-O-benzoyl-6-O-benzyl-beta-D-galactopyranosyl-(1-->4)-6-O-benzy l-2- deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (7), a key intermediate prepared by condensation of phenyl 6-O-benzyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (6) and 2,3,4-tri-O-benzoyl-6-O-benzyl-alpha-D-galactopyranosyl bromide (5), was glycosylated with methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside (8) to give the trisaccharide donor 9, which, on coupling with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-be ta-D- glucopyranoside (10), afforded the pentasaccharide 11. The regioselective glycosylation of 12 (derived by O-debenzoylation of 11) with 7 gave the heptasaccharide 13, which was converted by treatment with hydrazine monohydrate and subsequent N-acetylation into the hexasaccharide acceptor 14. The stereo- and regio-selective glycosylation of 14 with methyl (phenyl 5-acetamido-4,7,8,9-O-benzoyl-3,5-dideoxy-2-thio-D-glycero-beta-D-galact o-2- nonulopyranosid)onate (16) gave the desired octasaccharide 18. Hydrogenolytic removal of the benzyl groups in 18 and successive O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile gave the alpha-trichloro-acetimidate 21, which was then coupled with (2S,3R,4E)-2-azido-3-O-(tert-butyldiphenylsilyl)-4-octade cene-1,3-diol (22) to give 23. Compound 23 was transformed, via selective reduction of the azido group, N-introduction of octadecanoic acid, O-desilylation, O-deacylation, and saponification of the methyl ester group, into the title VIM-2 ganglioside 26.

Carbohydrate Sequence↗
PubMed1996

Gangliosides are neuronal ligands for myelin-associated glycoprotein.

Nerve cells depend on specific interactions with glial cells for proper function. Myelinating glial cells are thought to associate with neuronal axons, in part, via the cell-surface adhesion protein, myelin-associated glycoprotein (MAG). MAG is also thought to be a major inhibitor of neurite outgrowth (axon regeneration) in the adult central nervous system. Primary structure and in vitro function place MAG in an immunoglobulin-related family of sialic acid-binding lactins. We report that a limited set of structurally related gangliosides, known to be expressed on myelinated neurons in vivo, are ligands for MAG. When major brain gangliosides were adsorbed as artificial membranes on plastic microwells, only GT1b and GD1a supported cell adhesion of MAG-transfected COS-1 cells. Furthermore, a quantitatively minor ganglioside expressed on cholinergic neurons, GQ1b alpha (also known as Chol-1 alpha-b), was much more potent than GT1b or GD1a in supporting MAG-mediated cell adhesion. Adhesion to either GT1b or GQ1b alpha was abolished by pretreatment of the adsorbed gangliosides with neuraminidase. On the basis of structure-function studies of 19 test glycosphingolipids, an alpha 2,3-N-acetylneuraminic acid residue on the terminal galactose of a gangliotetraose core is necessary for MAG binding, and additional sialic acid residues linked to the other neutral core saccharides [Gal(II) and GalNAc(III)] contribute significantly to binding affinity. MAG-mediated adhesion to gangliosides was blocked by pretreatment of the MAG-transfected COS-1 cells with anti-MAG monoclonal antibody 513, which is known to inhibit oligodendrocyte-neuron binding. These data are consistent with the conclusion that MAG-mediated cell-cell interactions involve MAG-ganglioside recognition and binding.

Animals↗
PubMed1996

Synthesis of deoxygalactose-containing sialyl Le(X) ganglioside analogues to elucidate the structure necessary for selectin recognition.

Sialyl Lewis X ganglioside analogues containing 4-deoxy-, 6-deoxy-, and 4,6-dideoxy-D-galactopyranose in place of D-galactopyranose have been synthesized. Glycosylations of 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D-galactopyranoside and 2-(trimethylsilyl)ethyl beta-D-fucopyranoside with the phenyl 2-thioglycoside derivative of sialic acid, using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as the promoter in acetonitrile, gave the desired 2-(trimethylsilyl)ethyl sialyl-alpha-2-->3)-beta-D-galactopyranoside and -beta-D-fucopyranoside, respectively. The sialylgalactose derivative obtained was then modified to 4-deoxy and 4,6-dideoxy derivatives. These were converted, by O-benzoylation, transformation of the 2-(trimethylsilyl)ethyl group to trichloroacetimidates, and introduction of the methylthio group with methylthiomethylsilane, into the corresponding glycosyl donors, which were then coupled with 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1->3)-O-(2-acetamido-6-O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1->3)-2,4,6-tri-O-benzyl-beta-D- galactopyranoside in the presence of dimethyl(methylthio)sulfonium triflate (DMTST). The resulting pentasaccharides were each converted to the corresponding alpha-trichloroacetimidates, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the desired sphingosine derivatives. Selective reduction of the azide group, N-acylation with octadecanoic acid, O-deacylation, and saponification of the methyl ester afforded the target compounds.

Animals↗
PubMed1996

A highly practical synthesis of the sialyl Lewis X pentasaccharide and an investigation of binding to E-, P-, and L-selectins.

A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta OEt (1), as a potential blocker for E-selectin has been described. The glycosylation of a trisaccharide acceptor, Fuc alpha (1-3)GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, did not yield the desired sLex pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor, GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, quantitatively yielded the tetrasaccharide NeuAc alpha (2-3)Gal beta (1-4)GlcNAc beta (1-3)Gal beta OEt. This tetrasaccharide is readily converted to the title compound in a high yield by fucosylation, followed by deprotection. The inhibitory activities of compound 1 toward the binding of the natural ligand (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex tetrasaccharide.

Anti-Inflammatory Agents↗
PubMed1996

Synthesis and biological activities of three sulfated sialyl Le(x) ganglioside analogues for clarifying the real carbohydrate ligand structure of L-selectin.

Sulfated sialyl Le(x) ganglioside analogues at C-6 of D-galactose, N-acetyl-D-glucosamine, and of both D-galactose and N-acetyl-D-glucosamine residues have been synthesized, in order to clarify the structure of the real carbohydrate ligand of L-selectin. Coupling of the suitably protected N-acetyl-D-glucosaminyl-beta (1-->3)-lactose derivatives 13 and 16 with the sialyl alpha(2-->3)-D-galactopyranosyl trichloroacetimidates 10 and 12 (glycosyl donors), via glycosylation of 2-(trimethylsilyl)ethyl 4,6-O-benzylidene-beta-D-galactopyranoside (1) with the phenyl 2-thioglycoside derivative (2) of N-acetylneuraminic acid (Neu5Ac) using N-iodosuccinimide/TfOH, O-benzoylation, removal of the benzylidene group affording 5, selective 6-O-levulinoylation, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group, and imidate formation, or via O-acetylation of 5, removal of the 2-trimethylsilyl)ethyl group, then imidate formation, gave the pentasaccharides 18-20. The glycosylation of the pentasaccharide acceptors (21-23) derived from 18-20 by removal of the 4-methoxybenzyl group, with phenyl 1-thioglycoside derivative 27 of L-fucose using dimethyl(methylthio)sulfonium triflate (DMTST) afforded the corresponding hexasaccharides 28-30, which were transformed in good yields, via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with (2S,3R,4E)-2-azido-O-benzoyl-4-octadecene-1,3-diol (35) in the presence of boron trifluoride etherate, selective reduction of the azido group, coupling with octadecanoic acid, selective removal of the levulinoyl groups, treatment with sulfur trioxide-pyridine complex, then removal of the protecting groups, into the desired sulfated sialyl Le(x) ganglioside analogues 50-52.

Carbohydrate Conformation↗
PubMed1996

Inhibitory action of sulfatide, a putative ligand for L-selectin, on B cell proliferation and Ig production.

The interaction of L-selectin and its ligand is widely accepted to mediate leukocyte rolling and adhesion on the endothelial surface. Although L-selectin is ubiqultously expressed on lymphoid cells, its role in execution of lymphocyte functions is unknown. By flow cytometric analysis using mAb specific for sulfatide, a putative ligand for L-selectin, we found that sulfatide was selectively expressed on B cells, but not on T cells. To elucidate the involvement of L-selectin and its ligand in B cell activation, the present study was undertaken to investigate effects of sulfatide on T cell-dependent and -independent Ig production by B cells. In pokeweed mitogen-stimulated cultures, addition of sulfatide resulted in almost complete inhibition of Ig production by B cells in the presence of memory CD4+ T cells, whether L-selectin-positive or -negative. A similar inhibition of Ig production by sulfatide was found when B cells were stimulated with Staphylococcus aureus Cowan I and IL-2. Unlike sulfatide, a desulfated form of sulfatide, galactosylaceramide, did not show any effects on Ig production by B cells. Maximal inhibition of Ig production was observed when sulfatide was added at the early period of culture. Sulfatide suppressed effectively proliferation of B cells, but not of T cells. Sulfatide competed the binding of anti-L-selectin mAb to B cells, suggesting it could interfere B cell activation by blocking L-selectin function. The results suggest a novel role of the L-selectin/its ligand system in the initiation of B cell activation.

Adult↗
PubMed1995

Synthesis of sialyl Lewis X ganglioside analogues containing modified L-fucose residues.

Sialyl Le(x) ganglioside analogues containing 2-epi-, 2,3-di-epi-, 4-epi-, and 2-O-methyl-L-fucose in place of the L-fucose residue have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)- 2,4,6- tri-O-benzyl-beta-D-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective fucose analogues, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding protected 2-(trimethylsilyl)ethyl deoxy-alpha-L-hexopyranosyl-(1-->3)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-beta-D-galactopyrano sid es. These were transformed by reductive ring-opening of their benzylidene acetal groups into the glycosyl acceptors. Dimethyl (methylthio)sulfonium triflate-promoted glycosylation of these compounds with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D- galactopyranoside afforded the desired pentasaccharides, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding alpha-tri-chloroacetimidates. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol these in the presence of boron trifluoride etherate afforded the expected beta-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and deesterification, into the target gangliosides. The 2-(trimethylsilyl)ethyl glycosides of sialyl Le(x) oligosaccharides containing modified fucose were also prepared from the intermediates of the ganglioside synthesis.

Carbohydrate Sequence↗
PubMed1995

Synthetic and structural studies of alpha-sialyl-(2-->6) and alpha-sialyl-(2-->3) 1-deoxynojirimycin derivatives potentially useful for biomedical applications.

Suitably protected derivatives of 1-deoxynojirimycin (1,5-dideoxy-1,5-imino-D-glucitol, DNJ) and its D-galacto analog were coupled with 2-thioglycosides of N-acetylneuraminic acid. The resulting disaccharides were converted into a variety of alpha-sialyl-(2-->6)-and alpha-sialyl-(2-->3)-DNJ derivatives, including the cyclic lactams 6-O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyrano sylono- 1',5-lactam)-1,5-dideoxy-1,5-imino-D-glucitol and -D-galactitol. The structural features of the synthetic compounds were investigated by ion-spray mass and 1H NMR spectrometry. The 1C4 conformation of N-tert-butoxycarbonyl-DNJ, a synthetic intermediate having the gluco configuration, was confirmed by X-ray crystallography.

1-Deoxynojirimycin↗
PubMed1995

Immunosuppressive activity of chemically synthesized gangliosides.

New chemical synthetic methods have permitted the synthesis of a spectrum of glycosphingolipid molecular species, some of which are not naturally occurring. Here we have studied a number of chemically synthesized gangliosides for immunosuppressive activity, using a human in vitro specific antigen (tetanus toxoid)-induced assay of the cellular immune response. Chemically synthesized GM3 and GM4 had the same high degree of immunosuppressive activity as did natural GM3 and GM4 gangliosides, verifying that inhibition is intrinsic to the ganglioside molecules and not caused by other molecules sometimes found in natural preparations (e.g., proteins). Studies of modified molecular species of GM3 and GM4, also prepared by chemical synthesis, have shown the influence of certain structural details upon the immunosuppressive activity of gangliosides: (i) the inverse relationship between fatty acyl chain length and immunosuppressive activity is extended to even shorter chain lengths, with the synthetic gangliosides d18:1-C2:0-GM3 and d18:1-C14:0-GM3 being more immunosuppressive than d18:1-C18:0-GM3 and d18:1-C24:0-GM3; (ii) hydroxylation of the fatty acyl group decreases immunosuppressive activity; (iii) substitution of an S-glycosidic bond for an O-glycosidic bond in the sialic acid ketosidic linkage in GM4 does not alter its activity; and (iv) modifications of the sialic acid group variably influence immunosuppressive activity, since KDN-GM3 and -GM4 ganglioside analogues, which contain a 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid in place of N-acetylneuraminic acid, retain activity, while other modifications such as 8-epi-GM3, and to a lesser extent 9-deoxy-GM3, reduce immunosuppressive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Chemistry↗
PubMed1995

Sialidase of swine influenza A viruses: variation of the recognition specificities for sialyl linkages and for the molecular species of sialic acid with the year of isolation.

The sialidase of swine influenza A viruses of N1 and N2 subtypes, isolated from 1930 to 1992, was studied for substrate specificity with ganglio-series, lacto-series type II and GM3 gangliosides containing Neu5Ac alpha 2-3Gal, Neu5Gc alpha 2-3Gal and Neu5Ac alpha 2-6Gal linkages. All viral sialidases tested showed that the activity for hydrolysing substrates with Neu5Ac alpha 2-3Gal was higher than the activities with Neu5Gc alpha 2-3Gal and Neu5Ac alpha 2-6Gal linkages. When GM1b, GM3 and sialylparagloboside were used as substrates, the earliest strain (A/Wisconsin/15/30 H1N1, isolated in 1930) showed the activity ratio of Neu5Ac alpha 2-6Gal to Neu5Ac alpha 2-3Gal to be 0.13:0.2, and the ratio Neu5Gc alpha 2-3Gal/Neu5Ac alpha 2-3Gal to be 0.19:0.37, while those strains isolated from 1978 to 1992 exhibited ratios of 0.29:0.58 for Neu5Ac alpha 2-6Gal/Neu5Ac alpha 2-3Gal and 0.51:0.76 for Neu5Gc alpha 2-3Gal/Neu5Ac alpha 2-3Gal. The above results indicate that the substrate specificities of sialidases from swine influenza A viruses towards sialyl linkages and the molecular species of sialic acid are related to the year of isolation, i.e. strains isolated after 1978 exhibited higher activity towards Neu5Ac alpha 2-6Gal and Neu5Gc alpha 2-3Gal linkages when compared with strains isolated in an earlier year, 1930.

Animals↗
PubMed1995

Anti-inflammatory effects of sulfatides in selectin-dependent acute lung injury.

Selectins promote adhesive interactions between leukocytes and activated endothelial cells, the adhesion being mediated by 'counter-receptors' on endothelial cells and consisting of oligosaccharide conjugates containing sialic acid and fucose. There are also suggestions that selectins bind sulfated compounds, including sulfatides. Intravenous infusion of selectin-reactive oligosaccharides has been found to prevent selectin-dependent inflammatory lung injury. In the current studies using two models of neutrophil and selectin-dependent acute lung injury in rats, sulfatide and its modified versions were infused i.v. and the protective effects determined. Naturally occurring sulfatide, synthetic sulfatides and sulfated ganglioside were highly protective against lung injury following systemic activation of complement. Desulfated sulfatide was inactive. The protective effects of synthetic sulfatides required sulfation of galactose in position 3. Sulfatide was also protective in the IgG immune complex model of lung injury. The protective effects of sulfatides were associated with reduced content of myeloperoxidase (derived from neutrophils) in lung tissue. These data indicate that sulfatides have significant in vivo protective effects in neutrophil and selectin-dependent models of lung injury.

Animals↗
PubMed1995

Expression of endotoxic activities by synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents.

Synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents instead of the usual ester-branched acyl substituents were investigated for their biological activities. The activities were compared with those of a representative synthetic monosaccharide lipid A analog with an ester branch (GLA-60) and synthetic complete lipid A (506) to estimate the role of the attaching mode of the branched side chains for expression of endotoxic activities. Among the analogs with alkyl branches, GLA-146 and GLA-147, which have C12 and C14 alkyl side chains, respectively, showed strong endotoxic activities. These analogs exhibited comparable or stronger activities than those of GLA-60 in murine macrophage activation activities to induce mediators such as tumor necrosis factors, interleukin 6, and nitric oxide and in mitogenic activity towards murine spleen cells; however, these activities were weaker than the respective activities of 506. With respect to lethal toxicity to galactosamine-sensitized mice, the analogs showed stronger activity than that of GLA-60 and activity closer to that of 506. With respect to adjuvant activity, no significant activity was observed in the analogs, while the activities of GLA-60 and 506 were strong. When lipopolysaccharide-resistant C3H/HeJ mice were used, the activities described above were not observed either for the analogs under investigation nor for GLA-60 and 506. These findings indicate that the ester type of branch in lipid A and its analogs does not play an indispensable role in the expression of various endotoxic activities. However, it may play some role in the expression of adjuvant activity and in lowering the level of toxicity.

Adjuvants, Immunologic↗