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At least 19 recordsLinked to original sources
PubMed1992

Expression and regulation of L-selectin on eosinophils from human adults and neonates.

L-Selectin, previously known as LEC.CAM-1, LECAM-1, LAM1, and as the MEL-14, Leu-8, TQ1, and DREG-56 antigens, is a leukocyte membrane protein that participates in adhesion to endothelium. We studied its expression on eosinophils using flow cytometry and the MAb Dreg-56 and Leu-8. Unstimulated peripheral blood eosinophils from healthy adults expressed about one third the level of L-selectin as neutrophils (mean +/- SD specific fluorescence: 20.9 +/- 3.2 versus 54.5 +/- 8.4, p = 0.0001, n = 18). After stimulation with A23187, L-selectin expression on eosinophils was rapidly lost. This was temporally correlated with increased expression of Mac-1 (CD11b/CD18); the kinetics on eosinophils and neutrophils were similar. Eosinophil expression of L-selectin decreased modestly after stimulation with platelet activating factor, but was minimally affected by N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4, or C5a compared with their effects on neutrophils. Eosinophils from cord blood of healthy neonates born at term expressed less L-selectin than adult eosinophils (10.4 +/- 3.8 versus 19.4 +/- 2.7, p = 0.0001, n = 9); the relative reduction was the same as on cord blood neutrophils (36.4 +/- 8.2 versus 55.5 +/- 4.8, p = 0.0001, n = 9). Relative to baseline expression, the responses of neonatal and adult cells to stimulation did not differ. We conclude that neonatal eosinophils have abnormalities in L-selectin expression similar to neonatal neutrophils and suggest that decreased expression of L-selectin and a diminished responsiveness to direct stimulation with chemotactic factors are possible mechanisms that may limit the exudation of eosinophils.

Adult↗
PubMed1992

Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules.

High endothelial venules (HEV) lined by the high endothelium are the sites where leukocytes enter into the lymph nodes from the blood. Lymphocyte homing into lymph nodes is organ-selective, i.e., different molecules are involved in the lymphocyte homing to peripheral nodes compared with mucosa associated lymphoid tissue. The traffic into peripheral nodes is regulated by the expression of L-selectin on leukocytes and its ligand on HEVs. The ligand for L-selectin is suggested to be a 50, 90, or 105 kd glycoprotein, which is sulfated, fucosylated, and sialylated. The two other members of the selectin family (E- and P-selectin) recognize sialyl-Lewis x and -Lewis a (sLex and sLea, respectively) carbohydrate motifs, and there is preliminary data suggesting that this would also be the case for L-selectin. We have initiated a study to identify the expression of these sialylated structures on endothelial surfaces. We present data that show that HEVs in peripheral nodes, but not in the mucosa-associated lymphoid tissue, express large quantities of sLex and sLea identified by MAbs in immunohistology. Endothelium in capillaries or larger vessels in non-lymphoid tissues do not react with anti-sLex or -Lea mAbs. Only 1-2% of the lymphocytes in the peripheral blood express sLex and so far only the skin-homing lymphocytes are known to be sLex positive in larger quantities. We show that in many occasions the B cells in the peripheral lymph-node germinal centers are also sLex-, but not sLea-positive, and provide evidence of the restricted pattern of sLex and sLea expression on peripheral lymph-node HEVs. We propose that they are at least parts of the ligand for L-selectin.

Antibodies, Monoclonal↗
PubMed1992

The selectin family of carbohydrate-binding proteins: structure and importance of carbohydrate ligands for cell adhesion.

Protein-carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate-binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L-, E- and P-selectins, have domains homologous to other Ca(2+)-dependent (C-type) lectins. L-selectin is expressed constitutively on lymphocytes, E-selectin is expressed by activated endothelial cells, and P-selectin is expressed by activated platelets and endothelial cells. Here, we review the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L-selectin on leukocyte surfaces. In contrast, E- and P-selectins recognize specific carbohydrate determinants related to sialyl Le(x) antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitement among glycoconjugate researchers that other carbohydrate-binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions.

Amino Acid Sequence↗
PubMed1992

The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium.

OBJECTIVE: Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. METHODS: The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. RESULTS: Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL: CONCLUSION: These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.

Adult↗
PubMed1992

Neuropeptides promote neutrophil adherence to endothelial cell monolayers.

The objective of this study was to determine whether substance P and calcitonin gene-related peptide (CGRP), at physiologically relevant concentrations, affect leukocyte-endothelial cell adhesion. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated (40 min) with freshly isolated human neutrophils in the presence or absence of substance P or CGRP (10(-11) M). Both substance P and CGRP caused a significant increase (2-fold) in neutrophil adherence to HUVEC. Monoclonal antibodies (MAb) directed against the leukocyte adhesion glycoproteins CD11/CD18 (MAb IB4) and L-selectin (MAb DREG56) did not attenuate substance P-induced adhesion. Antibodies directed against the endothelial cell adhesion molecules E-selectin (MAb CL2) and ICAM-1 (MAb R6.5) were also without effect on substance P-induced neutrophil adhesion. Similar results were obtained when either MAb IB4, DREG56, CL2, or R6.5 was coincubated with CGRP-stimulated neutrophils and endothelial cells. Phorbol 12-myristate 13-acetate-stimulated neutrophil adherence was significantly attenuated by MAb IB4, indicating that CD11/CD18 participates in this adhesion process. The results of this study indicate that 1) the neuropeptides substance P and CGRP promote neutrophil adherence to venular endothelium and 2) the neuropeptide-induced adhesion is not mediated by the adhesion molecules CD11/CD18, L-selectin, E-selectin, or ICAM-1.

Antibodies, Monoclonal↗
PubMed1992

Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.

Antigens, CD↗
PubMed1992

Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM.

Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were > 2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or-DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM.

Adult↗
PubMed1992

Expression of integrins and other adhesion molecules in Epstein-Barr virus-transformed B lymphoblastoid cells and Burkitt's lymphoma cells.

Lymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell-surface adhesion molecules: integrins, immunoglobulin-related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), and on EBV-positive or EBV-negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the beta 1, beta 2 and beta 3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA-4), CD11a/CD18 (Leu-CAMa, LFA-1) and CD51/CD61 (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM-1) and CD58 (LFA-3) as well as the "homing receptors" L-selectin (LECAM-1) and CD44. BL lines had considerably lower amounts of VLA-4 than LCLs, and ICAM-1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.

Antibodies, Monoclonal↗
PubMed1992

Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets.

The glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes. It is a membrane component of cell storage granules, and is a member of the selectin family which includes E-selectin and L-selectin. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium. To evaluate the role of P-selectin in platelet-leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet-leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition.

Animals↗
PubMed1992

Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury.

Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset less than 1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (approximately 54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (approximately 41%), and CD11c (approximately 23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded approximately 27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Substrate specificity of the Trypanosoma cruzi trans-sialidase.

Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS). Here we study the substrate specificity of TS, which differs from all known sialyltransferases in that it does not require cytidine monophosphate (CMP)-SA as donor. The T. cruzi TS reversibly transfers SA to saccharides with terminal beta-Gal (but not alpha-Gal) residues. Donors are saccharides with SA linked to terminal beta-Gal residues by (alpha 2-3), but not (alpha 2-6) bonds. The type of beta-linkage of the terminal Gal residue is of minor importance (beta 1-4 and beta 1-6 are slightly better than beta 1-3), whereas chain length and the structure of additional vicinal sugar residues are not relevant. SA on the surface of living trypomastigotes of T. cruzi is transferred back and forth between the parasite surface and acceptor molecules with terminal beta-Gal, either in solution or on the surface of neighbouring mammalian cells. Addition of fucose residue on or close to the terminal galactose impairs TS activity. As a consequence, the enzyme acts poorly on the E-selectin ligand sialyl-Lewisx and its precursor Lewisx, and in vitro adhesion of TS-treated neutrophils to L-cells expressing L-selectin is not affected. Modifications in the structure of the (alpha 2-3)-linked N-acetyl-neuraminic acid (Neu5Ac) (deoxy or methoxy) of the donor molecules do not impair transfer if the changes are at C9, whereas changes at C4, C7 and C8 impair the ability to donate the modified SA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Molecular mechanism of blood monocyte adhesion to vascular endothelial cells.

The blood monocytes adhere to endothelial cells unstimulated and after stimulation by interleukin-1, tumor necrosis factor or other mediators. This process is mediated through specific molecules on both endothelial cells and monocytes. Using specific monoclonal antibodies and molecular cloning several families of molecules involved in leukocyte endothelial cell interaction have been defined. Leukocyte adhesion molecules include the three beta 2 integrins (CD11/CD18 molecules), VLA-4 and the L-Selectin. E-Selectin (ELAM-1), P-Selectin (GMP-140) and receptors of the immunoglobulin superfamily (ICAM-1, ICAM-2 and VCAM-1) are expressed on endothelial cells in basal conditions and after activation. It has been shown that these adhesive molecules are involved in blood monocyte adhesion to endothelial cells. Monocytes from patients with diabetes mellitus had an increased adhesion to endothelial cells in culture. As estimated by flow cytometry CD11b/CD18 expression on diabetic monocytes was increased. Pentoxifylline reduced CD11b/CD18 expression on normal and diabetic monocytes. This effect was associated to a decrease in monocyte adhesion to endothelial cells.

Cell Adhesion↗
PubMed1992

Oral polyvalent vaccine (Buccalin Berna) administration activates selected T-cell subsets and regulates the expression of polymorphonuclear leukocyte membrane molecules.

Acute respiratory tract infections (ARIS) still represent a major clinical problem during influenza outbreaks. The virus-induced impairment of the immune system favors the entry of opportunistic microorganisms into respiratory tract mucosa. A useful strategy to reduce ARIS is to provide at risk subjects an orally administrable polyvalent vaccine (OPV) comprised of bacteria strains recognised as the major ones responsible for ARIS. For the present study, the main circulating leukocyte populations of a group of healthy subjects receiving OPV were monitored as a marker of immune response. Subjects were investigated immediately before taking OPV (day 0) and 10,20, and 30 days later. Data show that T lymphocytes were induced to enhance the expression of class II MHC molecules, whilst a consistent number of CD4+ lymphocytes lost L-selectin, both phenomena indicating an activation status. OPV administration also modulated important molecules on the membrane of polymorphonuclear leukocytes, namely CD11b and CD16, strongly suggesting an activation of these cells and an enhancement of their defensive capacities. Finally, OPV was found to be able to increase the titer of serum antibodies specific for bacteria strains contained in the vaccine preparation in a portion of individuals. We conclude that OPV is able to consistently influence important immune functions and suggest that this property may be of relevance in preventing ARIS. Also, the present data may help to further our understanding of the mechanisms of OPV activity.

Administration, Oral↗
PubMed1992

Cell interaction molecules and cytokines which participate in B lymphopoiesis.

A molecular and cellular definition of the bone marrow microenvironment is rapidly contributing to our understanding of lymphohaemopoiesis. While lineage specific genes and their protein products are being identified, information is accumulating about mechanisms which may regulate their expression. Stimulation of B lymphocyte precursor replication, and other discrete functions, are being attributed to cytokines such as interleukin 7 (IL-7). The activity of these factors may be controlled at the level of synthesis, local concentration and interaction with extracellular matrix. Extremely small amounts of IL-7 are made by stromal cells, which are themselves being thoroughly studied as cloned cell lines. This in vitro characterization suggests that stromal cells can make at least 12 cytokines, that they can respond to some of those cytokines themselves, and that they retain differentiation potential. Several molecules have been identified which are probably required for recognition between cells in marrow. It is noteworthy that they belong to several previously described families of adhesion molecules and none is unique to that tissue. VCAM-1 is constitutively expressed on stromal cells in marrow and can be recognized by pre-B cells which bear the integrin VLA-4. The same pair of molecules is probably responsible for extravasation of leukocytes in other tissues during inflammation. Cell adhesion molecules are likely to work in a carefully coordinated and cooperative fashion. Their activity can be controlled by expression or, in some cases, modulated after display on the cell surface. For example, while most haemopoietic cells bear CD44, only certain cells utilize it for recognition of the ligand hyaluronate. The affinity for hyaluronate can be experimentally regulated and depends on the cytoplasmic domain of CD44. This capability for dynamic change may be important for transient interactions between cells, permitting movement of maturing precursors within and from marrow.

Animals↗
PubMed2026

TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sj&#xf6;gren's syndrome.

OBJECTIVES: This study aims to determine the role of acid&#x2011;sensitive nonspecific cation channels transmembrane protein 176A (TMEM176A) and TMEM176B in autoimmune diseases, with a focus on primary Sj&#xf6;gren's Syndrome (pSS). METHODS: We examined the expression patterns of TMEM176A and TMEM176B across tissues and cells utilizing bulk RNA-seq and scRNA-seq datasets. Immunophenotyping analysis was performed by flow cytometry to compare CD62L expression between TMEM176B&#x207a; and TMEM176B&#x207b; monocytes. The proportion of TMEM176B+ cells in monocytes was interrogated in both pSS patients and healthy controls. Clinical correlations of TMEM176B with anti&#x2011;SSB antibody and complement C4 levels were also evaluated. RESULTS: TMEM176A and TMEM176B showed conserved co&#x2011;expression and were significantly upregulated in autoimmune diseases. TMEM176B&#x207a; monocytes displayed higher CD62L positivity rate than TMEM176B- monocytes. In pSS patients, the proportion of TMEM176B&#x207a; monocytes was elevated in total monocytes, classical monocytes (cMo) and intermediate monocytes (iMo). The proportion of TMEM176B+ monocytes positively correlated with anti&#x2011;SSB levels, while several TMEM176B-associated monocyte subset markers inversely correlated with C4. CONCLUSION: TMEM176A and TMEM176B are highly correlated. TMEM176B expression in monocytes is linked to pSS and may serve as a novel auxiliary diagnostic biomarker.

Humans↗