Showing papers on "Galectin published in 1995"

Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex.

Abstract: Advanced glycation end products (AGE), the reactive derivatives of nonenzymatic glucose-protein condensation reactions, are implicated in the multiorgan complications of diabetes and aging. An AGE-specific cellular receptor complex (AGE-R) mediating AGE removal as well as multiple biological responses has been identified. By screening an expression library using antibody against a previously identified component of the AGE-R complex p90, a known partial cDNA clone was isolated with homology to galectin-3, a protein of diverse identity, and member of the galectin family. To explore this unexpected finding, the nature of the interactions between galectin-3 and AGE was studied using intact macrophage-like RAW 264.7 cells, membrane-associated and recombinant galectin-1 through -4, and model AGE-ligands (AGE-BSA, FFI-BSA). Among the members of this family (galectin-1 through 4), recombinant rat galectin-3 was found to exhibit high-affinity 125I-AGE-BSA binding with saturable kinetics (kD 3.5 × 107 M−1) that was fully blocked by excess unlabeled naturally formed AGE-BSA or synthetic FFI-BSA, but only weakly inhibited by several known galectin-3 ligands, such as lactose. In addition to the p90, immunoprecipitation with anti-galectin-3, followed by 125I-AGE-BSA ligand blot analysis of RAW 264.7 cell extracts, revealed galectin-3 (28 and 32 kD), as well as galectin-3-associated proteins (40 and 50 kD) with AGE-binding activity. Interaction of galectin-3 with AGE-BSA or FFI-BSA resulted in formation of SDS-, and β-mercaptoethanol-insoluble, but hydroxylamine-sensitive high-molecular weight complexes between AGE-ligand, galectin-3, and other membrane components. The findings point toward a mechanism by which galectin-3 may serve in the assembly of AGE-R components and in the efficient cell surface attachment and endocytosis by macrophages of a heterogenous pool of AGE moieties with diverse affinities, thus contributing to the elimination of these pathogenic substances.

Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages.

Abstract: A family of beta-galactoside-binding animal lectins has recently been designated as galectins. One member of this family, galectin-3, has been known as epsilon BP for its IgE-binding activity and as Mac-2, a macrophage surface antigen, CBP35, CBP30, L-29, and L-34. Although much information has accumulated on the expression of this lectin in murine macrophages and human monocytic cell lines, little is known about the expression and function of this protein in normal human monocytes/macrophages. We now report that galectin-3 is expressed in normal human peripheral blood monocytes and its level increases dramatically as human monocytes differentiate into macrophages upon culturing in vitro. Immunoblot analysis showed that there was a 5-fold increase in the level of galectin-3 after 1 day of culture and greater than a 12-fold increase after 5 days. Immunocytochemical analysis confirmed this progressive increase of galectin-3 expression in cultured monocytes. Immunogold cytochemistry/electron microscopy analysis revealed that galectin-3 was expressed on the surface of human monocytes and that the level of cell surface galectin-3 increased progressively as these cells differentiated into macrophages. The level of galectin-3 in human monocytes/macrophages was modulated by stimuli such as lipopolysaccharide and interferon-gamma, and galectin-3 was secreted when monocytes were stimulated by calcium ionophore A23187 Soluble galectin-3 caused superoxide release from human monocytes; this activity was dependent on the lectin property of galectin-3, as it was inhibitable by lactose. Thus, galectin-3 may modulate the function of this cell type in an autocrine or paracrine fashion through binding to cell surface glycoconjugates.

A human lectin, galectin-3 (epsilon bp/Mac-2), stimulates superoxide production by neutrophils.

Abstract: A family of soluble animal lectins, galectins, with beta-galactoside-binding activity, is gaining increased attention. One member of this family, galectin-3, has been previously designated by this group as epsilon bp, for its IgE-binding activity. On the basis of the saccharide specificity and other biochemical characteristics of epsilon bp, it is possible that this lectin could have an important extracellular modulatory role, functioning through recognition of critical cell surface glycoproteins on many cell types. We present evidence here that recombinant human epsilon bp activates human neutrophils in a dose-dependent manner as demonstrated by superoxide production. The observed activity is dependent on the lectin property of epsilon bp intrinsic to its carboxyl-terminal domain, as it could be inhibited effectively by lactose, a known saccharide ligand of epsilon bp. However, the amino-terminal domain is also necessary for the observed activity, as epsilon bp-C (the carboxyl-terminal domain fragment) is devoid of neutrophil-activating activity, even though it retains the carbohydrate-binding property. Affinity purification of lysates from cell surface-radio-iodinated neutrophils revealed two major protein bands of M(r) 115,000 and M(r) 180,000 that are recognized by epsilon bp and preliminary data suggested that one of these proteins is NCA-160, a human carcinoembryonic Ag-related glycoprotein. This study thus lends further support to our view of an extracellular function for epsilon bp and suggests that this protein has an important role in inflammation and host defense through modulating the function of neutrophils.

Carcinoembryonic Antigen and Other Glycoconjugates Act as Ligands for Galectin-3 in Human Colon Carcinoma Cells

Abstract: Galectin-1 and galectin-3, galactoside-binding lectins with molecular weights of M r 14,500 and 31,000, respectively, are expressed in normal and malignant cells and have been implicated in regulation of cell growth, adhesion, and metastasis. We analyzed the expression of galectins in 21 cultured human colon carcinoma cell lines by immunoblotting. Galectin-1 was detected in only 7, whereas galectin-3 was found in 20 of the cell lines. KM12 cells, which express only galectin-3, were used to isolate this lectin by affinity chromatography, and the purified lectin was used to identify complementary glycoconjugates by blotting. Galectin-3 was shown to bind to human laminin, carcinoembryonic antigen, and lysosome-associated membrane glycoproteins, which are involved in cell adhesion. Galectin-3 was localized on the KM12 cell surface and colocalized with carcinoembryonic antigen. Several endogenous glycoproteins and cell surface proteins of molecular weights in the range M r 58,000 to >200,000, including carcinoembryonic antigen and lysosome-associated membrane glycoproteins, were identified as galectin-3 ligands by coimmunoprecipitation with and affinity chromatography on immobilized galectin-3. These data demonstrate that galectin-3 interacts with several adhesion molecules and suggest that this lectin may have a role in human colon carcinoma cell adhesion.

Galectin-3 is expressed in the notochord, developing bones, and skin of the postimplantation mouse embryo.

Abstract: The galectins are a family of low molecular weight, calcium-independent mammalian carbohydrate binding proteins that exhibit specificity for beta-galactoside derivatives. We have examined the expression pattern of galectin-3 in the developing mouse embryo by in situ hybridisation and immunohistochemistry. In the embryo proper, galectin-3 message and protein are first detected in notochord, starting from 8.5 days post coitum (dpc), and persist until this structure disappears. Galectin-3 is later found in cartilage primordia and in developing skin from 13.5 dpc. This very restricted and dynamic pattern suggests that galectin-3 may participate in the establishment and/or maintenance of notochord as well as the formation of cartilage and differentiation of skin. Finally, we find that galectin-3, which is identical to the macrophage marker Mac-2, is also expressed in embryonic macrophages.

Expression of the endogenous 14-kDa beta-galactoside-binding lectin galectin in normal human skin.

Abstract: The localization of an endogenous 14-kDa beta-galactoside-binding lectin (galectin) and its pattern of gene expression were examined in normal human skin by light- and electron microscopy. Under the light microscope, immunostaining of 14-kDa galectin was observed in the cell membrane of cells in the basal and spinous layers of the epidermis. Galectin was also found in the Langerhans cells, as shown by double labeling using anti-14-kDa galectin and anti-CD1a antibodies. In the dermis, immunostaining for the 14-kDa galectin was positive in the extracellular matrix and fibroblasts. At the electron-microscopic level of resolution, galectin was located primarily along the plasma membrane of keratinocytes, and in both the cytoplasm and nucleus of Langerhans cells in the epidermis, whereas in the dermis it was detected in the extracellular matrix and in both the nucleus and cytoplasm of fibroblasts. The gene expression of 14-kDa galectin was visualized by the HRP-staining method following in situ hybridization techniques. The expression was detected in the cytoplasm of cells in the basal and spinous layers of the epidermis; whereas, in the dermis, it was detected in the cytoplasm of fibroblasts. Moreover, SDS-polyacrylamide gel electrophoresis and lectin-blot analysis revealed that this galectin bound to glycoproteins of approximately 17, 62, and 72 kDa in the epidermis and to those of 29, 54, and 220 kDa in the dermis. The present study indicates that 1) normal human skin produces the beta-galactoside-binding 14-kDa galectin, and 2) this galectin is located in both the epidermis, particularly in the keratinocytes and Langerhans cells, and in the dermis. These results suggest that galectin is important for cell-cell contact and/or adhesion in the epidermis and for cell-extracellular matrix interaction in the dermis.

Evidence for IgG autoantibodies to galectin-3, a beta-galactoside-binding lectin (Mac-2, epsilon binding protein, or carbohydrate binding protein 35) in human serum.

Abstract: Galectin-3 is a beta-galactoside-binding animal lectin formerly called epsilon protein, Mac-2, carbohydrate binding protein 35, CBH 30, L-29, or L34. The possible occurrence of autoantibodies to galectin-3 was investigated because crosslinking of galectins bound to IgE or Fc epsilon RI might produce mediator release from mast cells or basophils. Unexpectedly, a control serum from an individual free of current allergic symptoms was found to have a significantly elevated level of IgG anti-galectin-3 by ELISA employing galectin-3-coated wells incubated with test serum followed by HRPO-conjugated goat anti-human IgG. The reaction was not inhibitable by lactose, suggesting that it is not a result of binding of IgG by galectin-3 through lectin-carbohydrate interactions. The antibody activity was specifically adsorbed by galectin-3 and protein A-conjugated Sepharose and was associated primarily with subclass IgG1. The presence of the antibodies was confirmed by immunoblotting showing binding of IgG to the 30-kD galectin-3 band. The relevant epitopes were in the galectin-3 N-terminal domain. The propositus was subsequently found to have adenocarcinoma of the colon, and titers of IgG anti-galectin-3 were found to be sharply elevated after hemicolectomy. Similar antibody titers have not been found in family members, but small numbers of normal persons and patients with malignant neoplasms have been found to have evidence of IgG anti-galectin-3 antibodies at lower titers than the propositus. The pathogenesis of this autoimmune reaction is unclear, though there is a trend for it to occur in older persons.

Immune Reactions: Headlines, Overviews, Tables and Graphics

Abstract: 1 Cytokines, Growth Factors, Chemokines and their receptors.- 1.1 Overview.- 1.1.1 Cytokines in Hematopoiesis.- 1.1.2 Classification of Growth Factors.- 1.1.3 Receptors for Cytokines.- 1.1.4 Receptors for Growth Factors.- 1.1.5 Characteristics of Chemokines.- 1.1.6 Neutrophil-Activating Peptides.- 1.2 Characteristics of Mediators, Receptors.- 1.2.1 SCF, IL-1, IL-1 RA.- 1.2.2. IL-2.- 1.2.3 IL-3, IL-4, IL-5, IL-6.- 1.2.4 LIF, IL-7, IL-8.- 1.2.5 IL-10, IL-11, IL-12, IL-13.- 1.2.6 GM-CSF, G-CSF, M-CSF, Erythropoietin, Thrombopoietin, IFN Gamma.- 1.2.7 IGF, TNF, TGF, PDGF, EGF, FGF.- 1.2.8 Oncostatin, CNTF.- 1.2.9 Approaches to Inhibit the Biological Effect of Growth Factors.- 2 Cell-Adhesion Molecules.- 2.1 Overview.- 2.1.1 Classification.- 2.1.2 Function.- 2.2 Characteristics.- 2.2.1 Immunoglobulin Gene Superfamily Type.- 2.2.2 Integrin Type.- 2.2.3 Cell Distribution.- 2.2.4 Binding Partners.- 2.2.5 Modulation of Expression and Function.- 2.2.6 Structure and Function of CD44.- 2.2.7 Structure and Function of Cadherins.- 3 Antigen Presentation.- 3.1 Overview.- 3.2 Details.- 3.2.1 Dendritic Cells.- 3.2.2 Antigen-Binding Molecules.- 3.2.3 MHC Genes.- 3.2.4 Regulation of MHC Gene Expression.- 3.2.5 Loading of Antigen-Presenting Molecules.- 3.2.6 Antigen Presentation by B-Cells.- 3.2.7 Expression of MHC Molecules.- 3.2.8 Modulation of Expression of MHC Molecules.- 4 Differentiation of T-Cells.- 4.1 Overview.- 4.2 Details.- 4.2.1 T-Cell Development.- 4.2.2 The T-Cell Receptor.- 4.2.3 The CD4 Molecule.- 4.2.4 The CD8 Molecule.- 4.2.5 Activation of T-Cells by Antigen-Presenting Cells.- 4.2.6 Signal Transduction After Activation of the TCR Complex.- 4.2.7 Activation of T Cells.- 4.2.8 Activation of Memory T-Cells.- 4.2.9 Pharmacological Intervention of T-Cell Activation.- 5 Superantigens.- 5.1 Overview.- 5.1.1 Comparison Between Conventional Antigens and Superantigens.- 5.1.2 Function.- 5.2 Details.- 5.2.1 Foreign Superantigens.- 5.2.2 Self-Superantigens of Mouse Mammary Tumor Virus (MMTV).- 6 Differentiation of B-Cells.- 6.1 Overview.- 6.2 Details.- 6.2.1 B-Cell Development.- 6.2.2 The B-Cell Receptor.- 6.2.3 Transcriptional Control of Ig Heavy- and Ig Light-Chain Genes.- 7 Antibody Formation.- 7.1 Overview.- 7.2 Details.- 7.2.1 VDJ Recombination.- 7.2.2 Cooperation of B-Cells with T Cells.- 7.2.3 B-Cell Differentiation in Lymph Nodes.- 7.2.4 Main Cytokines Involved in Differentiation to Plasma Cells.- 8 Fc Receptors and Antibody Interaction.- 8.1 Overview.- 8.2 Details.- 8.2.1 Properties of Murine Fc Receptors.- 8.2.2 Human Fc Receptors.- 8.2.3. Modulation by Cytokines.- 8.2.4 Release of Immunoglobulin Binding Proteins (IBFs) and Its Modulation.- 8.2.5 Blockage of Antibody Production.- 9 Generation of the IgA Response.- 9.1 Overview.- 9.2 Details.- 9.2.1 Properties of Secretory and Serum IgA.- 9.2.2 Circulation and Metabolization of IgA.- 9.2.3 Enteral IgA Response.- 9.2.4 Secretory Immunoglobulin A (sIgA) in Tears.- 10 Complement Activation and Inhibition.- 10.1 Overview.- 10.1.1 Classification.- 10.1.2 Activation.- 10.1.3 Blockage of Comlement Mediated Lysis by Nucleated Cells.- 10.2 Details.- 10.2.1 Function of Complement Inhibitors.- 10.2.2 Activity of Complement Split Products on Cells.- 10.2.3 Complement Receptors.- 10.2.4 Interactions Between Complement Components and Platelets.- 10.2.5 Resistance of Nucleated Cells (NC) to Lysis by Membrane Attacking Complex (MAC) of Complement.- 10.2.6 Activation of Nucleated Cells by Membrane Attacking Complex.- 10.2.7 Diseases Associated with Inherited or Acquired Deficiency of Complement Components.- 10.2.8 Approaches for Immunotherapy with Regulators of Complement Activation.- 11 Cell-Mediated Cytotoxicity.- 11.1 Overview.- 11.2 Details.- 11.2.1 Cytotoxicity by T-Lymphocytes.- 11.2.2 Cellular Cytotoxicity via Mechanisms Not Involving Recognition of Antigens Presented by MHC-1.- 12 Immune-Mediated Inflammatory Reaction.- 12.1 Overview.- 12.1.1 Cascades of the Inflammatory Response.- 12.1.2 Central Role of the Hageman Factor.- 12.1.3 Complexity of Interactions (Cells, Cytokines, Mediators).- 12.2 Details.- 12.2.1 Activation and Action of Kinins.- 12.2.2 Biological Action of Mediators of the Arachidonic Acid Pathway.- 12.2.3 Diseases Associated with Prominent Neutrophil Infiltrates.- 12.2.4 Metabolic Changes Induced by Cytokines.- 12.2.5 Putative Mechanism of the Delayed-Type Hypersensitivity Reaction.- 12.2.6 Approaches for the Therapy of Inflammatory Reactions.- 13 Interactions with Endothelial Cells.- 13.1 Overview.- 13.1,1 Granulocytes and Endothelial Cells.- 13.1.2 Lymphocytes and Endothelial Cells.- 13.2 Details.- 13.2.1 Activation of Endothelial Cells.- 13.2.2 Endothelium-Derived Relaxing Factors (EDRF).- 13.2.3 Endothelium-Derived Contracting Factors (EDCF).- 13.2.4 Immunological Aspects of Artheriosclerosis.- 14 Involvement of the Clotting System and Platelets.- 14.1 Overview.- 14.2 Details.- 14.2.1 Inhibition of Coagulation in Normal Epithelium.- 14.2.2 Effect of Growth Factors and Cytokines on Plasminogen Activator Secretion.- 14.2.3 Activation and Aggregation of Platelets.- 14.2.4 Role of Transforming Growth Factor-?.- 14.2.5 Arachidonic Acid Metabolism in Platelets.- 14.2.6 Inhibitors of Platelet Aggregation.- 14.2.7 Modulation of Platelet Aggregation In Vivo.- 14.2.8 Cytokines that Stimulate Megakaryocytopoiesis.- 15 Enzymatic Degradation of Extracellular Matrix.- 15.1 Overview.- 15.1.1 Destruction of Extracellular Matrix.- 15.1.2 Interaction of Proteases.- 15.2 Details.- 15.2.1 Matrix Metalloproteinases (MMP).- 15.2.2 Cellular Proteases.- 15.2.3 Modulation of Secretion of Cellular Proteases.- 16 Angiogenesis.- 16.1 Overview.- 16.2 Details.- 16.2.1 Angiogenic or Mitogenic Peptides.- 16.2.2 Vascular Endothelial Growth Factor.- 16.2.3 Balance Between uPA/PAT 1 and FGF/TGF-?.- 16.2.4 Inhibitors of Angiogenesis.- 17 Systemic Inflammatory Reaction Syndrome.- 17.1 Overview.- 17.2 Details.- 17.2.1 Pathophysiological Pathways.- 17.2.2 Role of LBS Binding Protein.- 17.2.3 Role of Complement and Neutrophils.- 17.2.4 Approaches to Influencing SIRS.- 18 Immune Complex Mediated Diseases.- 18.1 Overview.- 18.2 Details.- 18.2.1 Conformational Change of Antibody.- 18.2.2 Effector Function of Immunoglobulins.- 18.2.3 Size of Immune Complexes.- 18.2.4 Inhibition/Solubilization of IC by Complement.- 18.2.5 Elimination of IC.- 18.2.6 IC Diseases Associated with Changes in the Expression of CR-1, CR-2, CR-3, C-IA (INH).- 18.2.7 Approaches for Therapy of IC Diseases.- 19 Allergic Diseases.- 19.1 Overview.- 19.2 Details.- 19.2.1 Modulation of IgE Secretion by Cytokines.- 19.2.2 Allergic Inflammation.- 19.2.3 Role of Langerhans Cells.- 19.2.4 Role of Fc? RII (CD23).- 19.2.5 Histamine-Releasing Factors (HRF).- 19.2.6 Treatment of Allergic Diseases.- 20 Autoimmune Diseases.- 20.1 Overview.- 20.1.1 Reasons for Autoimmune Reactions.- 20.1.2 Autoantibodies in Normal Persons.- 20.1.3 Role of B-Cells and T-Helper Cells in Autoimmune Diseases.- 20.2 Details.- 20.2.1 Specificity of Human Autoantibodies.- 20.2.2 Relationship to Exposure to Xenobiotics.- 20.2.3 Approaches to Treat Autoimmune Diseases.- 21 Immune Suppression.- 21.1 Overview.- 21.1.1 Therapeutic Activity and Toxicity of Immune Suppressives.- 21.1.2 Mode of Action of Immune Suppressive Drugs.- 21.2 Details.- 21.2.1 Mode of Action of Specific Agents.- 21.2.2 Monoclonal Antibodies.- 22 Immune Reaction in Neoplasia.- 22.1 Overview.- 22.2 Details.- 22.2.1 Human Tumor Antigens Detected by Immune Response.- 22.2.2 Viruses Associated with Cancer.- 22.2.3 Vaccines for Prophylaxis of Virus-Induced Tumors.- 22.2.4 Tumors and Infiltrating Macrophages.- 22.2.5 Tumors and Infiltrating Lymphocytes.- 22.2.6 Tumor Therapy with Cytokines.- 22.2.7 Active Specific Therapy with "Tumor Vaccines".- 22.2.8 Mechanisms by Which Tumor Cells Become "Immune Resistant".- 22.2.9 Tumor Therapy with Antibody Preparations.- 22.2.10 Targeting of Drugs with Monoclonal Antibodies to Malignant Cells.- 22.2.11 Reasons for the Limited Success of Antibodies.- 22.2.12 Pharmacokinetic Parameters for Antibodies.- 22.2.13 Antibody-Dependent Enzyme-Mediated Prodrug Therapy.- 22.2.14 Antibody Engineering.- 23 CNS and Immune Reactions.- 23.1 Overview.- 23.2 Details.- 23.2.1 Modulation of the Immune System by Neuropeptides.- 23.2.2 IL-1 as a "Neuropeptide".- 23.2.3 Cytokines and Cytokine Receptors expressed by Cells of the CNS and Endocrine Organs.- 23.2.4 Communication of the CNS with the Immune System.- 23.2.5 Modulation of the Endocrine System by Immune Mediators.- 23.2.6 Hormonal Influence on Antibodies in Mucosal tissues.- 23.2.7 Immune Response and Epilepsy.- 24 Genetic Background of Apoptosis and Malignant Lymphocyte Growth.- 24.1 Apoptosis and Malignant Lymphocyte Growth.- 24.2 Mechanisms of Tumorigenesis.- 25 Somatic Gene Therapy.- 25.1 Overview.- 25.1.1 Opportunities and Risks.- 25.1.2 Preconditions.- 25.1.3 Methods.- 25.2 Details.- 25.2.1 Viral Transfer of Genes.- 25.2.2 Liposomal Transfer of Genes.- 25.2.3 Receptor Mediated Transfer of Genes.- 25.2.4 Experimental Therapeutic Approaches.- 25.2.5 Immunization with Polynucleotides.- 26 CD Terminology.- References.