Glycosylation-dependent cell adhesion molecule 1: a novel mucin-like adhesion ligand for L-selectin.
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Animals↗
Biomedical subjects
M S Singer
Publications and source records attributed to M S Singer.
Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo.
During the inflammatory response, granulocytes and other leukocytes adhere to and emigrate from small venules. Before firm attachment, leukocytes are observed rolling slowly along the endothelium in venules of most tissues accessible to intravital microscopy. The molecular mechanism underlying this early type of leukocyte-endothelial interaction is unknown. Leukocyte rolling was investigated in venules (diameter, 40 microns) of the exposed rat mesentery. Micro-infusion of a recombinant soluble chimera (LEC-IgG) of the murine homing receptor lectin-like cell adhesion molecule 1 (LEC-CAM 1; gp90MEL) into individual venules reduced the number of rolling leukocytes by 89% +/- 2% (mean +/- SEM, n = 20 venules), while a similar CD4 chimera (CD4-IgG) had no effect (inhibition 14% +/- 7%, n = 25). Rolling was also greatly reduced by a polyclonal serum against LEC-CAM 1 (inhibition 84% +/- 3%, n = 35); preimmune serum was ineffective (11% +/- 13% inhibition, n = 28). These findings indicate that LEC-CAM 1 mediates the adhesive interaction underlying leukocyte rolling and thus may play an important role in inflammation and in pathologic conditions involving leukocytes.
Animals↗
Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor.
Lymphocyte attachment to high endothelial venules within lymph nodes is mediated by the peripheral lymph node homing receptor (pnHR), originally defined on mouse lymphocytes by the MEL-14 mAb. The pnHR is a calcium-dependent lectin-like receptor, a member of the LEC-CAM family of adhesion proteins. Here, using a soluble recombinant form of the homing receptor, we have identified an endothelial ligand for the pnHR as an approximately 50-kD sulfated, fucosylated, and sialylated glycoprotein, which we designate Sgp50 (sulfated glycoprotein of 50 kD). Recombinant receptor binding to this lymph node-specific glycoprotein requires calcium and is inhibitable by specific carbohydrates and by MEL-14 mAb. Sialylation of the component is required for binding. Additionally, the glycoprotein is precipitated by MECA-79, an adhesion-blocking mAb reactive with lymph node HEV. A related glycoprotein of approximately 90 kD (designated as Sgp90) is also identified.
Animals↗
A lymphocyte homing receptor (L-selectin) mediates the in vitro attachment of lymphocytes to myelinated tracts of the central nervous system.
Lymphocytes enter lymph nodes by first adhering to high endothelial venules, an adhesive event mediated by a lectinlike lymphocyte receptor (L-selectin). Previously, it was shown with an in vitro assay that lymphocytes preferentially adhere to myelin-rich regions in brain sections. Here, using a recombinant form of L-selectin as an immunohistochemical reagent, we demonstrate potential ligands for L-selectin in myelinated regions of the central but not the peripheral nervous system. Using several antibodies and phorbol ester downmodulation of the receptor, we establish that L-selectin on human lymphocytes has a primary involvement in lymphocyte adherence to the myelinated regions. On mouse lymphocytes, the contribution of L-selectin appears to be partial. These findings raise the possibility that leukocyte targeting to myelin-rich regions, via a L-selectin dependent mechanism, may be a factor in the pathogenesis of certain central nervous system demyelinating diseases.
Animals↗
Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets.
Platelet GMP-140, along with ELAM-1 and gp90MEL, comprise the LEC-CAM family of cell-cell adhesion proteins. The three proteins demonstrate a highly related domain organization, which includes an extracellular calcium-type lectin motif. gp90MEL, a lymphocyte homing receptor, mediates lymphocyte attachment to high endothelial venules of lymph nodes through recognition of a sialylated ligand on the endothelial cells. The rosetting of neutrophils or promyelocytic HL60 cells by activated platelets is mediated by GMP-140 on the platelets. We show here that treatment of neutrophils or HL60 cells with 3 broad spectrum sialidases completely prevents rosetting. However, the Newcastle disease virus sialidase, an enzyme specific for alpha 2,3 and alpha 2,8 linkages of sialic acid does not affect rosetting of HL60 cells. These results indicate that the ligand for GMP-140 requires sialic acid and suggest that an alpha 2,6 linkage may be critical.
Blood Platelets↗
Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor.
Considerable evidence implicates gp90MEL as a lymphocyte homing receptor mediating lymphocyte attachment to high endothelial venules of lymph nodes in mouse. The protein appears to function as a calcium-dependent, lectin-like receptor as inferred primarily by the ability of specific carbohydrates to block its function and by the presence of a calcium-type lectin domain in its primary sequence. An ELISA assay is described which provides the first demonstration that the isolated protein has lectin activity and allows a further definition of its carbohydrate specificity. In addition to the monosaccharides mannose-6-phosphate and fructose-1-phosphate, ligand activity is shown for the sulfated glycolipid, sulfatide, and for two sulfated fucose-containing polysaccharides (fucoidin and egg jelly coat) from nonmammalian sources.
Animals↗
Requirement for sialic acid on the endothelial ligand of a lymphocyte homing receptor.
The entry of blood-borne lymphocytes into most secondary lymphoid organs is initiated by a highly specific adhesive interaction with the specialized cuboidal endothelial cells of high endothelial venules (HEV). The adhesive receptors on lymphocytes that dictate interactions with HEV in different lymphoid organs are called homing receptors, signifying their critical role in controlling organ-selective lymphocyte migration. Considerable work has established that the mouse peripheral lymph node homing receptor (pnHR), defined by the mAb MEL-14, functions as a lectin-like adhesive protein. We have previously shown that sialidase treatment of peripheral lymph node (PN) HEV abrogates lymphocyte attachment to the HEV both in vivo and in vitro. We extend this evidence by demonstrating that Limax agglutinin (LA), a sialic acid-specific lectin, when reacted with HEV exposed in cryostat-cut tissue sections, blocks lymphocyte attachment to PN HEV and, unexpectedly, to the HEV of Peyer's patches (PP) as well. Using a recombinant form of the pnHR as a histochemical probe for its cognate adhesive site (HEV-ligand) on PN HEV, we demonstrate that both sialidase and Limax agglutinin functionally inactive this ligand. It is concluded that the requirement for sialic acid is at the level of the pnHR interaction with its HEV ligand. A distinct sialyloligosaccharide may encode the recognition determinant of a PP HEV ligand.
Animals↗
Cloning of a lymphocyte homing receptor reveals a lectin domain.
Lymphocytes express cell surface molecules, termed homing receptors, that mediate their selective attachment to specialized high endothelial venules found within secondary lymphoid organs. Previous work has demonstrated that the adhesive interaction between lymphocytes and the endothelium of peripheral lymph nodes appears to involve a lectin-like activity. Moreover, MEL-14, a monoclonal antibody that blocks lymphocyte-peripheral lymph node binding and presumably recognizes the homing receptor mediating this adhesive interaction, appeared to detect the lectin-like receptor. In this paper we describe the cloning of a murine cDNA that encodes the antigen recognized by the MEL-14 antibody. Characterization of the cDNA encoding the putative mouse peripheral lymph node-specific homing receptor shows that it contains a lectin domain that appears to be involved in the binding of lymphocytes to peripheral lymph node endothelium, thus defining a new type of cellular adhesion molecule. This result supports a novel mechanism for the distribution of lymphocyte populations to various lymphoid organs.
Amino Acid Sequence↗
Intravenously injected sialidase inactivates attachment sites for lymphocytes on high endothelial venules.
Blood-borne lymphocytes initiate entry into secondary lymphoid organs, such as peripheral lymph nodes (PN) and gut-associated Peyer's patches (PP), by a highly specific adhesive interaction between the lymphocytes and the endothelium of specialized blood vessels known as a high endothelial venules (HEV). The selectivity with which functional subpopulations of lymphocytes migrate into particular lymphoid organs is believed to be regulated by the expression of cell adhesion receptors and complementary ligands on lymphocytes and HEV, respectively. The entry of lymphocytes into PN and PP has clearly been shown to involve distinct receptor-ligand pairs. Employing the Stamper-Woodruff in vitro adhesion assay, which measures lymphocyte attachment to HEV in cryostat-cut sections of lymphoid organs, we have previously shown that treatment of PN sections with two different sialidases inactivates HEV-adhesive ligands, whereas treatment of PP tissue sections has no effect on HEV-adhesive function. We now report that in vivo exposure of HEV to sialidase (after i.v. injection of the enzyme) also selectively prevents subsequent in vitro attachment of lymphocytes to PN HEV but not to PP HEV. Consistent with this organ-selective impairment of HEV-adhesive function by sialidase, i.v. injection of the enzyme is shown to prevent short term lymphocyte accumulation within peripheral lymph nodes while having no significant effect on accumulation in PP, blood, or nonlymphoid organs. Histologic examination with the sialic acid-specific lectin from Limax flavus verified that i.v. injected sialidase effectively removes stainable sialic acid moieties from HEV in both PN and PP. This study confirms that sialic acid is required for the adhesive function of PN HEV-ligands. A role for sialic acid as either a recognition determinant or as a regulatory molecule can be envisioned. In view of the fact that many pathogens release sialidase and cause substantially elevated serum levels of this enzyme, the present observations may have pathophysiologic significance. One mechanism by which such pathogens may avoid destruction is to inactivate susceptible HEV-ligands and disrupt the entry of lymphocytes into lymphoid organs where immune responses against the pathogens would normally be initiated.
Animals↗
The perception of poverty and wealth among teenage university students.
This study is concerned with the perception of poverty and wealth among teenage university students. Two hundred twenty students completed a questionnaire which probed their perceptions of the attributions and consequences of poverty and wealth, requested them to estimate the job prospects of a school leaver with and without a certificate qualification, and also requested that they estimate the income for both a specified "poor" and "rich" man. The students also provided information about their economic preferences, religious position, and family financial position. Results indicate that the sample emphasized the significance of the family and placed little weight on luck when dealing with poverty and wealth. The sample emphasized the economic consequences of poverty and wealth, and did not rate their psychological consequences as being of much importance. Certain groups within the sample showed some deviations in their perceptions. The most substantial group differences were between the capitalist-religious and socialist-religious groups.
Adolescent↗
Absence of a hemispheric superiority in the recognition of European and Asian faces.
The present study was designed to examine whether there is a difference in hemispheric superiority in the recognition of European and Asian faces. A visual hemifield-presentation technique involving monocular testing was employed. Ten European subjects were presented a recognition task involving European faces and 10 other European subjects a similar task involving Asian faces. The data indicated no hemispheric superiority in either case; however, subjects made significantly more errors in recognising Asian faces than European faces in both visual hemifields.
Dominance, Cerebral↗
Causal attributions, perceived consequences of unemployment, and perceptions of employment prospects among adolescents in New Zealand.
The present study investigated the causal attributions and perceived consequences of unemployment, as well as perceptions of employment prospects, among high school students in New Zealand. A sample of Form 4 (Grade 9) boys (M age 14.3 years) and girls (14.4 years) and a sample of Form 6 and 7 (Grades 11 and 12) boys (16.9 years) and girls (16.6 years) were tested. No sex or age differences were found in students' causal attributions about unemployment. Societal factors were judged as the most important cause for unemployment. Luck was considered the least important reason. Form 4 students placed a greater emphasis on economic consequences, whereas Form 6 and 7 students regarded social consequences as more important. The consistency in the present findings and those from studies in other countries suggests that cross-cultural similarities do exist in adolescents' perceptions of unemployment.
Adaptation, Psychological↗
Age stereotypes as a function of profession.
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Adolescent↗
Involvement of sialic acid on endothelial cells in organ-specific lymphocyte recirculation.
Mouse lymphocytes incubated on cryostat-cut sections of lymphoid organs (lymph nodes and Peyer's patches) specifically adhere to the endothelium of high endothelial venules (HEV), the specialized blood vessels to which recirculating lymphocytes attach as they migrate from the blood into the parenchyma of the lymphoid organs. Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV. These results suggest that sialic acid on endothelial cells may be an organ-specific recognition determinant for lymphocyte attachment.
Animals↗
Isolation of a teratocarcinoma stem cell lectin implicated in intercellular adhesion.
We have previously identified a cell surface teratocarcinoma stem cell lectin with a fucan/mannan specificity. We now report the purification of the hemagglutinin (lectin) from stem cell conditioned medium by exclusion on a Sepharose 2B column, followed by elution with 0.5M NaCl from DEAE-cellulose, providing an overall purification of about 90-fold. When this material was analyzed, by SDS-polyacrylamide gel electrophoresis, a major band of Mr 56000 was consistently observed. Hemagglutination activity was renatured from the gels and localized exclusively to a region of the gel that, as detected by fluorography, contains only the 56-kDa component. This suggested that this polypeptide comprises the lectin.
Animals↗
The perception of poverty and wealth among teenagers.
This study is concerned with the perception of poverty and wealth among high-school teenagers. Over 300 teenagers completed a questionnaire which probed their perceptions of the attributions and consequences of poverty and wealth, and requested them to estimate the income for both a specified "poor" and "rich" man. The results indicate that all groups in this sample emphasized the significance of the family and downplayed the significance of luck when dealing with poverty and wealth. Further, the groups emphasized the economic consequences of poverty and wealth and they did not rate their psychological consequences as being of much importance. The results are discussed in terms of the small literature relevant to this topic.
Adolescent↗
Teratocarcinoma stem cell adhesion: the role of divalent cations and a cell surface lectin.
We describe two additive systems of intercellular adhesion in teratocarcinoma stem cells (Nulli cell line). One component is divalent cation-dependent (Ca++ or Mg++) and the other involves a cell surface fucan/mannan-specific lectin, previously identified on stem cells by an erythrocyte rosetting assay. The existence of these two systems is inferred from the observation that reaggregation of stem cells was partially inhibited by the removal of divalent cations or by the presence of lectin inhibitors such as fucoidan, but reaggregation was completely blocked when the two conditions were combined. Our results are related to recent work describing a calcium-dependent system of intercellular adhesion in teratocarcinoma stem cells.
Animals↗
A fucan specific lectin on teratocarcinoma stem cells.
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Animals↗