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R Renkonen

Publications and source records attributed to R Renkonen.

At least 37 records · Page 2Linked to original sources
PubMed1997

A time-resolved immunofluorometric method for the measurement of sialyl Lewis x-synthesizing alpha1,3-fucosyltransferase activity.

We describe here an assay that employs a highly sensitive nonradioactive method, time-resolved fluorometry, for measuring the activity of the enzyme GDP-Fuc:NeuNAcalpha2-3Galbeta1-4GlcNAc-R (Fuc to GlcNAc) alpha1,3-fucosyltransferase (alpha1,3FT). In this assay, a neoglycoprotein substrate of alpha1,3FT is immobilized on a microtiter plate. Incubation with the fucose donor GDP-fucose and enzyme source converts the acceptor NeuNAcalpha2-3Galbeta1-4GlcNAc-R to the product NeuNAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc-R, which is quantified using a product-specific (antisialyl Lewis x) primary antibody and europium chelate-labeled secondary antibody. In the development of the assay, we used extracts of alpha1,3FT-transfected insect cells as the specific enzyme source. The reaction product formation was proportional to time of incubation (0-2 h) and the extract added (0.1-10 microU of enzyme) and was dependent on the GDP-fucose and glycoconjugate acceptor. We have also demonstrated with different cultured cancer cell lines that this time-resolved immunofluorometric assay allows rapid measurement of alpha1,3FT activity from a large number of crude cell lysate samples. Our results indicated that cell lines which expressed more sialyl Lewis x determinant on their surfaces had higher levels of alpha1,3FT activity. The advantages of this new assay are high sensitivity and a wide linear range of measurement. The assay is expected to be useful in the determination of regulation mechanisms of sialyl Lewis x-synthesizing alpha1,3-fucosyltransferases.

Flow Cytometry↗
PubMed1997

L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion.

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. alpha (1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.

Animals↗
PubMed1997

In vitro experimental studies of sialyl Lewis x and sialyl Lewis a on endothelial and carcinoma cells: crucial glycans on selectin ligands.

Extravasation from the blood of malignant tumour cells that form metastasis and leukocytes that go into tissues require contact between selectins and their sialyl Lewis x and sialyl Lewis a (sLe(x) and sLe(a) respectively) decorated ligands. Endothelial cells have been shown to express sLe(x) epitopes in lymph nodes and at sites of inflammation, and this is crucial for the selectin-dependent leukocyte traffic. Besides the ability to synthesize sLe(x) on sialylated N-acetyllactosamine via the action of alpha(1,3)fucosyltransferase(s), endothelial cells can also degrade sLe(x) to Lewis x through the action of alpha(2,3)sialidase(s). In addition, several epithelial tumors possess the machinery to synthesize sLe(x), which facilitates their adhesion to endothelial E- and P-selectin.

Animals↗
PubMed1997

Synthesis of a new nanomolar saccharide inhibitor of lymphocyte adhesion: different polylactosamine backbones present multiple sialyl Lewis x determinants to L-selectin in high-affinity mode.

Lymphocyte infiltration is a hallmark of acute rejections in solid organ transplants, such as cardiac allograft. We have previously shown that lymphocyte extravasation to cardiac grafts undergoing rejection is largely due to interactions between lymphocyte L-selectin and its sialyl Lewis x (sLex) decorated ligands. Our previous work demonstrated further that an enzymatically synthetized tetravalent sLex glycan of a branched polylactosamine backbone is a highly efficient inhibitor of L-selectin-dependent lymphocyte adhesion to graft endothelium. To improve the availability of multivalent sLex glycans for anti-inflammatory indications, we now report enzymatic synthesis of another tetravalent sLex glycan that can be potentially produced on a large scale, and show that even the new saccharide is a nanomolar inhibitor of L-selectin-dependent lymphocyte adhesion. The novel antagonist is sLex beta 1-3' (sLex beta 1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc (8) (where LacNAc is the disaccharide Gal beta 1-4GlcNac and sLex is the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-4 (Fuc alpha 1-3) GlcNAc). Its five-step synthesis was started from the octameric polylactosamine LacNAc beta 1-3' (GlcNAc beta 1-6') LacNAc beta 1-3' (GlcNAc beta 1-6') LacNAc (3), which in turn is accessible in one step from the hexasaccharide LacNAc beta 1-3'LacNAc beta 1-3'LacNAc. Importantly, the hexasaccharide primer has been synthesized chemically (Alais and Veyrieres, Tetrahedron Lett., 24, 5223, 1983). Hence, our data outline a route to glycan 8, consisting of a combination of chemical and enzymatic methods of oligosaccharide synthesis. In addition, our data show that polylactosamine backbones are able to present multiple sialyl Lewis x determinants to L-selectin in high-affinity mode, without a requirement for uniqueness in the backbone structure.

Amino Sugars↗
PubMed1996

Synthesis of a tetravalent sialyl Lewis x glycan, a high-affinity inhibitor of L-selectin-mediated lymphocyte binding to endothelium.

Kidney transplant rejection is an inflammatory process characterized by lymphocyte infiltration. Our earlier observations have shown that peritubular capillary endothelium (PTCE) is the site of lymphocyte entry into the rejecting renal allograft. During rejection, PTCE begins to express sialyl Lewis x de novo, and binds lymphocytes by a mechanism largely dependent on L-selectin. Hence, inhibiting the lymphocyte-endothelial interaction with oligosaccharide ligands of L-selectin offers an attractive possibility to prevent the inflammation and rejection. Here, we report enzyme-assisted synthesis of N-acetyllactosamine-based tetra-, deca-, and docosameric saccharides carrying one, two or four distally located sialyl Lewis x groups [Neu-NAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc] (sLex), respectively. When tested for their ability to inhibit lymphocyte-endothelial interaction during rat kidney transplant rejection, all sLex-saccharides were inhibitors in the Stamper-Woodruff binding assays; the analogues lacking fucose showed no inhibitory potency. The tetravalent sLex glycan proved to be a high-affinity adhesion inhibitor with an IC50 < 50 nM. While less powerful than the tetravalent glycan, also the divalent sLex saccharide was a much better inhibitor than the monovalent glycan. Hence, increasing multivalency and, possibly, increasing chain length of the polylactosamine backbone, enhances the inhibitory potency of sLex bearing glycans in the lymphocyte-endothelial adhesion assay. This suggests that L-selectin behaves as a "functional oligomer" on lymphocyte surfaces.

Animals↗
PubMed1996

Targeting of active rat alpha 2,3-sialyltransferase to the yeast cell wall by the aid of the hsp 150 delta-carrier: toward synthesis of sLe(x)-decorated L-selectin ligands.

Interactions between selectins and their oligosaccharide-decorated ligands play a crucial role in the initiation of leukocyte extravasation. We have shown that synthetic multivalent sialyl Lewis x glycans inhibit strongly the adhesion of lymphocytes to endothelium at sites of inflammation. However, enzyme-assisted synthesis of these oligosaccharides si hampered by the lack of sufficient amounts of specific glycosyltransferases. We report here the construction of Saccharomyces cerevisiae strains expressing the soluble catalytic ectodomain of rat Gal(beta)1-3/4GlcNac alpha 2,3-sialyltransferase (ST3Ne) fused to the C-terminus of the hsp150 delta-carrier polypeptide. The hsp150 delta-carrier, which is an N-terminal fragmented of a natural secretory protein of yeast, is able to confer secretion-competence to several heterologous proteins, which otherwise remain in the yeast endoplasmic reticulum. The ST3Ne portion of the hsp 150 delta-ST3Ne fusion protein adopted an enzymatically active conformation and was N-glycosylated and disulfide-bonded. Hsp150 delta-ST3Ne was secreted with a half-time of about 7.5 min and remained intercalated in the cell wall, which covers the yeast plasma membrane. About 110 mU of sialyltransferase per litre was produced in 16 h. Whole live yeast cells were able to transfer sialic acid from CMP-NeuNAc to N-acetyllactosamine yielding alpha 2,3-sialyl-N-acetyllactosamine, as evidenced by paper chromatography, cleavage by linkage-specific sialidase, and NMR analysis. Our data suggest that yeast cells externalizing mammalian glycosyltransferases with the aid of the hsp150 delta-carrier could provide a source of enzymes for synthesis of valuable oligosaccharides.

Acetylglucosamine↗
PubMed1995

Synthesis of a divalent sialyl Lewis x O-glycan, a potent inhibitor of lymphocyte-endothelium adhesion. Evidence that multivalency enhances the saccharide binding to L-selectin.

The recognition of cell-surface L-selectin by its carbohydrate ligands causes lymphocytes to roll on capillary endothelium at sites of inflammation. As this primary contact is a prerequisite for extravasation of the leukocytes to the tissue, its inhibition by free oligosaccharides capable of competing with the natural L-selectin ligands in an attractive therapeutic possibility. The exact structures of the biological ligands of L-selectin are not yet known, but the principal carbohydrate epitopes share some structural features: they are O-glycosidically linked mucin-type oligosaccharides with N-acetyllactosamine backbone, which is 3'-sialylated or 3'-sulfated, 3-fucosylated and sometimes 6- or 6'-sulfated at the distal N-acetyllactosamine termini. Multivalency of the ligand, which is believed to enhance the binding, is achieved by a branched polylactosamine backbone or by a clustered array of O-glycans. We report here enzymic synthesis of a large oligosaccharide fulfilling several of the features characteristic to the L-selectin ligands: it is a dodecameric O-glycosidic core-2-type oligosaccharide alditol with a branched polylactosamine backbone carrying two distal alpha-2,3'-sialylated and alpha-1,3-fucosylated N-acetyl-lactosamine groups (sialyl Lewis x, sialyl Le(x)). The structure of each saccharide on the synthesis route from disaccharide Gal beta 1-3GalNAc to the dodecasaccharide alditol was established by several methods including one- and two-dimensional 1H-NMR spectroscopy. The last step of the synthesis, the alpha-1,3-fucosylation of the 6-linked arm proceeded sluggishly, and was associated with a noticeable shift in H1 resonance of the GlcNAc residue of the branch-bearing N-acetyllactosamine unit. The final synthesis product and its analogs lacking one or both of the fucose residues were tested as inhibitors of L-selectin-mediated lymphocyte-endothelium interaction in vitro in rejecting rat kidney transplant. While the non-fucosylated O-glycosidic oligosaccharide alditol did not possess any inhibitory activity, the mono-fucosylated one (i.e. monovalent sialyl Le(x)) prevented the binding significantly and the difucosylated dodecasaccharide alditol (i.e. divalent sialyl Le(x)) was a very potent inhibitor (IC50, inhibitory concentration preventing 50% of binding = 0.15 microM). Besides the multivalency, also the Gal beta 1-3GalNAc-ol sequence of the O-glycosidic core appeared to increase the affinity of the glycan to L-selectin. This was indicated by parallel inhibition experiments, where a disialylated and difucosylated branched polylactosamine decasaccharide, similar to the divalent dodecasaccharide alditol, but lacking the reduced O-glycosidic core, was a less effective inhibitor (IC50 = 0.5 microM) than the O-glycosidic dodecasaccharide alditol.

Animals↗
PubMed1995

Expression and function of alpha 2,3-sialyl- and alpha 1,3/1,4-fucosyltransferases in colon adenocarcinoma cell lines: role in synthesis of E-selectin counter-receptors.

We show here that colon-carcinoma cell lines adhere to E-selectin via sialyl Lewis x and sialyl Lewis a (s(Lex) and s(Lea)) oligosaccharides and that this adhesion can be enhanced by TNF stimulation. To study in greater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of s(Lex) and s(Lea on cancer cells. These oligosaccharides are synthesized by sequential action of alpha 2,3 sialyl (alpha 2,3-ST) and alpha 1,3/1/4 fucosyltransferases (alpha 1,3/1,4-FT) on existing (poly)N-acetyllactosamine chains. We report here that mRNAs of 2 recently cloned alpha 2,3-STs and 4 alpha 1,3/1,4-FTs are expressed in adenocarcinoma cells. In functional assays alpha 2,3-ST and alpha 1,3- or 1,4-FT activities were observed in adenocarcinoma cell lysates to exogenous N-acetyllactosamine and lacto-N-biose acceptors and to their sialylated derivatives, leading to the synthesis of the sialyl-N-acetyllactosamine and s(Lex) or the sialyllacto-N-biose and s(Lea), respectively. Furthermore, the inflammatory cytokine TNF could enhance some alpha 2,3-ST and alpha 1,3/1,4-FT activities capable of generating E-selectin counter-receptors. Taken together, these data show that COLO 205 and HT-29 adenocarcinoma cell lines adhere to E-selectin in a TNF-inducible manner via their cell-surface s(Lex) and s(Lea). These cells also express mRNA as well as inducible enzyme activities of several alpha 2,3-STs and alpha 1,3/1,4-FTs responsible for the final steps in the synthesis of s(Lex) and s(Lea).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.

Acute organ transplant rejection is characterized by a heavy lymphocyte infiltration. We have previously shown that alterations in the graft endothelium lead to increased lymphocyte traffic into the graft. Here, we demonstrate that lymphocytes adhere to the endothelium of rejecting cardiac transplants, but not to the endothelium of syngeneic grafts or normal hearts analyzed with the in vitro Stamper-Woodruff binding assay. Concomitant with the enhanced lymphocyte adhesion, the cardiac endothelium begins to de novo express sialyl Lewis(a) and sialyl Lewis(x) (sLea and sLex) epitopes, which have been shown to be sequences of L-selectin counterreceptors. The endothelium of allografts, but not that of syngeneic grafts or normal controls, also reacted with the L-selectin-immunoglobulin G fusion protein, giving further proof of inducible L-selectin counterreceptors. The lymphocyte adhesion to endothelium could be significantly decreased either by treating the lymphocytes with anti-L-selectin antibody HRL-1, or by treating the tissue sections with sialidase or anti-sLea or anti-sLex monoclonal antibodies. Finally, we synthetized enzymatically several members of the sLex family oligosaccharides and analyzed their ability to block lymphocyte adhesion to cardiac endothelium. The monovalent sLex (a tetramer), divalent sLex (a decamer), and tetravalent sLex (a 22-mer) could all significantly reduce lymphocyte binding, but the inhibition by the tetravalent sLex-construct was clearly superior to other members of the sLex family. The crucial control oligosaccharides, sialyl lactosamines lacking fucose but being otherwise similar to the members of sLex family, had no effect on lymphocyte binding.

Animals↗
PubMed1995

Alpha E beta 7 and alpha 4 beta 7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages.

The two beta 7 integrins alpha E beta 7 and alpha 4 beta 7 are the most recently described members of the integrins participating in intercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found in lymphocytes associating with the epithelium. Expression of beta 7 has mainly been studied on lymphocytes whereas macrophages have been reported not to express the beta 7 integrins. In this paper we have studied the expression of beta 7 integrins in monocytoid cells. The myelomonocytic cell lines HL-60 and THP-1 did not express beta 7 mRNA or protein, but differentiation of these cell lines to macrophages with phorbol 12-myristate 13-acetate (PMA) led to a strong induction of the beta 7 mRNA expression. A clear but less pronounced up-regulation of beta 7 mRNA-expression was also seen after treatment of HL-60 and THP-1 cells with interferon-gamma (IFN-gamma). However, its up-regulating effect on the surface expression of alpha 4 beta 7 and alpha E beta 7 complexes (detected by the monoclonal antibodies Act I and HML-1, respectively) exceeded that observed with PMA. To verify the in vitro cell line observations with normal cells, we also studied peripheral blood monocytes and tissue macrophages. Peripheral blood monocytes were Act I- and HML-1- in flow cytometry, but their expression was increased after a 72-h culture in the presence of PMA or IFN-gamma. Also, several Act I+ and HML-1+ macrophages were found in immunohistochemical stainings of both liver and edemic lung biopsies as well as in lymph node sinuses. We therefore conclude that while monocytes do not express beta 7 integrins the more differentiated cells of the monocyte-macrophage lineage do express both the alpha 4 beta 7 and alpha E beta 7 integrins, which might play a role in their intraepithelial homing.

Antibodies, Monoclonal↗
PubMed1994

Genistein enhances the ICAM-mediated adhesion by inducing the expression of ICAM-1 and its counter-receptors.

Binding of circulating cells to endothelium is mediated by recognition between endothelial adhesion molecules and their counter-receptors. The beta 2 integrins are a group of adhesion molecules, mainly expressed on leukocytes, that mediate intercellular binding by recognizing their counterparts on endothelial cells, among others ICAM-1. In this study we have studied the regulation of this interaction in myelomonocytic cells treated with genistein, a tyrosine kinase inhibitor with several other biological functions. We show that genistein upregulates the surface expression of the beta 2-integrins in the monoblastic THP-1 and to a lesser extent in the promyelocytic HL-60 leukemia cell lines. This upregulation leads to an increase in the adherence of THP-1 cells to ICAM-1. Genistein also modulates the expression of ICAM-1 on endothelial cells by potentiating the upregulating effect of TNF and IFN-gamma. Genistein may thus enhance intercellular binding by affecting both the endothelium and the circulating cells.

Antigens, CD↗
PubMed1994

In vivo evidence of the role of alpha 4 beta 1-VCAM-1 interaction in sarcoma, but not in carcinoma extravasation.

Tumor-cell invasion can occur via either lymphatics or blood vessels. When in the blood circulation, tumor cells have to adhere to endothelium lining the blood vessels before they can extravasate. Several families of adhesion molecules have been recognized: selectins and their oligosaccharide-containing ligands and integrins and their counter-receptors belonging to the immunoglobulin superfamily. Besides their essential role in leukocyte extravasation, these adhesion molecules have been proposed by vitro experiments to be involved in tumor-cell invasion by facilitating the adhesion of malignant cells to endothelium leading to extravasation and metastasis. We have previously shown that, in vitro, several sarcoma cell lines adhere strongly to cultured endothelial cells via alpha 4 beta 1-VCAM-1 interaction. Here we show that sarcoma cells, especially in the metastatic lesions, were strongly alpha 4 beta 1 positive but did not express alpha 4 beta 7, which is another receptor for VCAM-I. Furthermore, we demonstrate that the capillary endothelium within metastatic sarcoma lesions reacted strongly with anti-VCAM-I antibody and very often the alpha 4 beta 1-expressing sarcoma cells were localized in the close vicinity of VCAM-I-expressing vessels. As control material we analyzed carcinoma specimens, but could not detect any alpha 4-integrin expression on malignant cells even though the endothelial cells were often VCAM-I positive. These results suggest that carcinomas do not use alpha 4 beta 1-VCAM-I in extravasation and, taken together, provide circumstantial evidence that in vitro findings of alpha 4 beta1-VCAM-I-dependent sarcoma cell adhesion to endothelium can be extended to in vivo situations.

Adenocarcinoma↗
PubMed1994

Characterization of the E-selectin ligand on NK cells.

In this study we demonstrate that human CD56+CD16+/CD3- NK cells adhere to the E-selectin expressed by stimulated HUVEC in a sialidase- and Ca(2+)-dependent manner, and express a silylated Lex adhesion structure. We have characterized this sLe(x) epitope on NK cell in detail and show here that the sLe(x) on NK cells was not recognized by the CSLEX1 Ab, but was readily identified by two anti-di-sLe(x) Abs, KM-93 and FH-6. Furthermore, cleaving sialic acid with a sialidase treatment revealed a pool of Le(x) epitopes on the NK cells surface, providing further proof that NK cells express sLe(x) epitopes. Extensive protease treatments did not cleave the sLe(x) epitope from NK cells, which suggests that it could be linked to a lipid backbone. This di-sLe(x) was able to mediate adhesion to E-selectin, suggesting that it represents an essential part or is closely related to a selectin ligand on NK cells. We were also able to show that NK cells possess several alpha 2,3 sialyltransferases and alpha 1,3 or alpha 1,3/4 fucosyltransferases. These enzymes are crucial in the synthesis of sLe(x) epitopes on cell surfaces. Taken together, we provide evidence that NK cells have a di-sLe(x) oligosaccharide capable of adhesion to E-selectin, and NK cells have the machinery (i.e., relevant transferases) to generate these sialylated Lewis oligosaccharides.

Calcium↗
PubMed1994

Alpha 2,3-sialyl and alpha 1,3-fucosyltransferase-dependent synthesis of sialyl Lewis x, an essential oligosaccharide present on L-selectin counterreceptors, in cultured endothelial cells.

Sialyl Lewis x (sLex) oligosaccharides have been shown to be present in counterreceptors for L-selectin. We and others have previously shown that high endothelial cells in lymph nodes and at sites of inflammation express sLex. Here we show that also cultured human umbilical vein endothelial cells (HUVEC) express sLex on their cell surface. This oligosaccharide is formed by sequential action of alpha 2,3-sialyl- (alpha 2,3-ST) and alpha 1,3-fucosyltransferases (alpha 1,3-FT) on N-acetyllactosamine. At least two of the several alpha 2,3-ST and four of the several alpha 1,3-FT are present in HUVEC. In functional assays both alpha 2,3-ST and alpha 1,3-FT activities were observed in HUVEC lysates with exogenous lactosamine and sialyllactosamine acceptors, leading to the generation of the sialyllactosamine and sLex sequences, respectively. TNF stimulation increased the level of mRNA expression of FT VI, and the alpha 1,3-FT activity in HUVEC. Taken together these data show that endothelial cells express sLex and that they possess mRNA as well as enzyme activities of several alpha 2,3-ST and alpha 1,3-FT necessary in the final steps of sLex synthesis. Furthermore, inflammatory cytokines such as TNF can enhance transferase activities relevant in generating putative L-selectin counterreceptors.

Cell Adhesion Molecules↗
PubMed1994

Expression of six protein kinase C isotypes in endothelial cells.

Protein kinase C (PKC) family is an important regulatory element in signal transduction, cellular regulation and tumor promotion. The classical PKC isotypes (alpha, beta and gamma) are Ca(2+)-dependent and can be activated by diacylglycerol. The novel isotypes, PKC delta, PKC epsilon, PKC eta (L) and PKC theta, are Ca(2+)-independent, whereas the two atypical PKCs (zeta and lambda) lack the Ca(2+)-binding region and are not activated by diacylglycerol. Here we show that cultured human endothelial cell line EA.hy926 as well as freshly isolated human umbilical vein endothelial cells express members of all PKC subfamilies. No traces of PKC gamma or delta were detected in endothelial cells. On the contrary the classical PKCs (alpha and beta), the novel PKC epsilon, as well as the atypical PKC zeta are present at the mRNA level in human endothelial cells and the corresponding proteins are also detected by immunoblotting.

Cell Line↗
PubMed1994

Human NK cells expressing alpha 4 beta 1/beta 7 adhere to VCAM-1 without preactivation.

The authors demonstrate that resting CD56+/CD3- NK cell adhesion to the endothelial VCAM-1 is over three-fold higher than CD56-/CD3+ T-cell adhesion. T-cell, but not NK-cell adhesion, to VCAM-1 is enhanced significantly by stimulation. The expression of VCAM-1 receptor subunits alpha 4 and beta 1 on both effector cells remains unchanged upon stimulation. A subpopulation of NK cells, as well as of T cells, was found to express beta 7, whose expression was not altered upon stimulation. The authors conclude that the adhesive properties of the same receptor structures on these distinct cell populations are regulated in a different manner, according to the specific functions of the effector cells of the immune system.

Antigens, Neoplasm↗
PubMed1994

Alkali-treated LPS of Yersinia enterocolitica does not induce expression of E-selectin, ICAM-1 or VCAM-1 on endothelial cells but may mediate antibody- and complement-dependent cell injury.

Lipopolysaccharide (LPS) prepared from a rough mutant of Salmonella typhimurium and deacylated enzymatically (dLPS) does not promote neutrophil adherence to human umbilical vein endothelial cells (HUVECs). This paper reports that similarly, a smooth form of LPS prepared from Yersinia enterocolitica O:3, a serotype known to trigger reactive arthritis in humans, and treated with alkali (yersinia LPS-OH) failed to augment neutrophil adherence to HUVECs. Studies of the mechanism underlying the poor augmentation revealed that neither enzymatically deacylated LPS from Escherichia coli J5 (J5 dLPS) nor yersinia LPS-OH stimulated expression of endothelial cell adhesion molecules E-selectin, VCAM-1 and ICAM-1, whereas both intact J5 LPS and yersinia LPS were stimulatory. Impaired up-regulation could not be explained by decreased binding of yersinia LPS-OH to HUVECs. Furthermore, 51Cr-labelled HUVECs treated with different concentrations of yersinia LPS-OH released 51Cr in the presence of anti-yersinia anti-O antibody and complement. J5 dLPS and yersinia LPS-OH inhibited up-regulation of the adhesion molecules induced by J5 LPS and yersinia LPS but not that induced by tumour necrosis factor alpha. Taken together, the results suggest that although yersinia LPS-OH can depress development of acute inflammation by inhibiting up-regulation of endothelial-cell adhesion molecules, sufficient LPS-OH is bound to induce cell injury and thereby inflammation in the presence of specific antibody and complement. The findings may have pathogenetic implications in yersinia-triggered reactive arthritis characterized by dissemination of yersinia LPS throughout the body.

ABO Blood-Group System↗