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Blood Reviews Dec 1992Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their... (Review)
Review
Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their functional roles include the hydrolysis of several biologically active peptides and growth factors and some have proved to be of diagnostic and prognostic value in leukaemia. These enzymes may also be found in serum as a consequence of non-haematopoietic related diseases and so have been used as indicators of liver damage. Haematopoietic cells in the bone marrow go through a process of growth and differentiation before being released into the peripheral circulation where they fulfill many functional roles. The enzyme activities of some aminopeptidases have been shown to modulate the growth of these cells. In addition, the activities of these enzymes themselves can be regulated by haematopoietic growth factors. However, the mechanisms that regulate their expression and activity are not fully understood. In this report the current literature has been reviewed for evidence of expression, regulation and clinical significance.
Topics: Aminopeptidases; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD13 Antigens; Cell Differentiation; Enzyme Induction; Hematopoietic Stem Cells; Humans; Oncogenes; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fes; Substrate Specificity
PubMed: 1362509
DOI: 10.1016/0268-960x(92)90020-q -
Biochimica Et Biophysica Acta Dec 1998The two migration inhibitory factor- (MIF)-related protein-8 (MRP8; S100A8) and MRP14 (S100A9) are two calcium-binding proteins of the S100 family. These proteins are... (Comparative Study)
Comparative Study Review
The two migration inhibitory factor- (MIF)-related protein-8 (MRP8; S100A8) and MRP14 (S100A9) are two calcium-binding proteins of the S100 family. These proteins are expressed during myeloid differentiation, are abundant in granulocytes and monocytes, and form a heterodimeric complex in a Ca2+-dependent manner. Phagocytes expressing MRP8 and MRP14 belong to the early infiltrating cells and dominate acute inflammatory lesions. In addition, elevated serum levels of MRP8 and MRP14 have been found in patients suffering from a number of inflammatory disorders including cystic fibrosis, rheumatoid arthritis, and chronic bronchitis, suggesting conceivable extracellular roles for these proteins. Although a number of possible functions for MRP8/14 have been proposed, the biological function still remains unclear. This review addresses recent developments regarding the MRP14-mediated promotion of leukocyte-endothelial cell-interactions and the characterization of MRP8/14 heterodimers as a fatty acid binding protein complex. In view of the current knowledge, the authors will hypothesize that MRP8 and MRP14 play an important role in leukocyte trafficking, but do not affect neutrophil effector functions.
Topics: Amino Acid Sequence; Animals; Antigens, Differentiation; Calcium-Binding Proteins; Calgranulin A; Calgranulin B; HL-60 Cells; Humans; Inflammation; Molecular Sequence Data; Neutrophil Activation; S100 Proteins; Sequence Homology, Amino Acid
PubMed: 9920411
DOI: 10.1016/s0167-4889(98)00144-x -
Clinical and Experimental Immunology Sep 2007Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative... (Review)
Review
Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10-15% of all cases of CVID and it is highly likely that further genetic defects will be identified.
Topics: Antigens, CD19; Antigens, Differentiation, T-Lymphocyte; Common Variable Immunodeficiency; Genetic Predisposition to Disease; Humans; Inducible T-Cell Co-Stimulator Protein; Transmembrane Activator and CAML Interactor Protein
PubMed: 17697196
DOI: 10.1111/j.1365-2249.2007.03461.x -
Kidney International. Supplement Sep 2000The advanced glycosylation end product (AGE)-binding proteins identified so far include the components of the AGE-receptor complex p60, p90 and galectin-3, receptor for... (Review)
Review
The advanced glycosylation end product (AGE)-binding proteins identified so far include the components of the AGE-receptor complex p60, p90 and galectin-3, receptor for advanced glycosylation end products (RAGE), and the macrophage scavenger receptor types I and II. Galectin-3 interacts with beta-galactoside residues of several cell surface and matrix glycoproteins through the carbohydrate recognition domain and is also capable of peptide-peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the modulation of cell adhesion, the control of cell cycle, and the mRNA splicing activity. Moreover, in macrophages, astrocytes, and endothelial cells, galectin-3 has been shown to exhibit a high-affinity binding for AGEs; the lack of a transmembrane anchor sequence or signal peptide suggests that it associates with other AGE-receptor components rather than playing an independent role as AGE-receptor. In tissues that are targets of diabetic vascular complications, such as the mesangium and the endothelium, galectin-3 is not expressed or only weakly expressed under basal conditions, at variance with p90 and p60 but becomes detectable with aging and is induced or up-regulated by the diabetic milieu, which only slightly affects the expression of p90 or p60. This (over)expression of galectin-3 may in turn modulate AGE-receptor-mediated events by modifying the function of the AGE-receptor complex, which could play a role in the pathogenesis of target tissue injury. Up-regulated galectin-3 expression may also exert direct effects on tissue remodeling, independently of AGE ligands, by virtue of its adhesive and growth regulating properties.
Topics: Animals; Antigens, Differentiation; Cell Adhesion; Cell Cycle; Diabetes Complications; Galectin 3; Glycation End Products, Advanced; Humans; RNA Splicing
PubMed: 10997688
DOI: 10.1046/j.1523-1755.2000.07706.x -
Current Opinion in Allergy and Clinical... Feb 2013Siglec-8 and Siglec-F are single pass transmembrane inhibitory receptors found on the surface of human and mouse eosinophils, respectively, but very little is known... (Review)
Review
PURPOSE OF REVIEW
Siglec-8 and Siglec-F are single pass transmembrane inhibitory receptors found on the surface of human and mouse eosinophils, respectively, but very little is known about their physiologic glycan ligands. This article reviews the latest knowledge on this topic and outlines the strategies being used to further define the production and glycobiochemical nature of these molecules in the lung.
RECENT FINDINGS
Both Siglec-8 and Siglec-F recognize the same glycan structure, namely 6'-sulfated sialyl Lewis X, as determined using glycan array technologies. Studies have identified α2,3-linked sialylated glycoprotein structures localized to mouse airway epithelium in tissue sections, where their constitutive expression requires the specific sialyltransferase St3gal3. Expression of these ligands in lung is enhanced during allergic inflammation and by cytokines such as IL-13, and is maintained in primary air-liquid interface cultures of mouse lung epithelium. Further characterization suggests that they are high molecular weight sialylated proteins, putatively mucins. By combining analytic glycomics, glycoproteomic mapping, and further in-vitro eosinophil experimentation including the ability of candidate structures to enhance eosinophil apoptosis, a finely detailed appreciation of the structural requirements for productive Siglec-8 and Siglec-F engagement should soon emerge.
SUMMARY
An enhanced understanding of Siglec-F, Siglec-8, and their ligands should improve our understanding of endogenous lung pathways limiting the survival of eosinophils within the airway in diseases such as asthma. Knowledge of this biology may also result in novel opportunities for drug development involving glycans and glycomimetics that selectively bind to Siglec-8 and induce eosinophil death.
Topics: Animals; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; Asthma; Eosinophils; Humans; Lectins; Ligands; Lung; Mice; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 23160308
DOI: 10.1097/ACI.0b013e32835b594a -
Blood Jun 2012Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute... (Review)
Review
Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multipotent CD33(-) stem cells as well others arising from, or predominantly involving, committed CD33(+) myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Clinical Trials as Topic; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Models, Biological; Molecular Targeted Therapy; Neoplastic Stem Cells; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome
PubMed: 22286199
DOI: 10.1182/blood-2011-11-325050 -
Immunology Jun 2001
Review
Topics: Animals; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; B-Lymphocytes; Cell Adhesion Molecules; Cell Communication; Humans; Immune System; Lectins; Mice; N-Acetylneuraminic Acid; Sialic Acid Binding Ig-like Lectin 2; Sialic Acid Binding Ig-like Lectin 3; Sialic Acid Binding Immunoglobulin-like Lectins; Signal Transduction
PubMed: 11412300
DOI: 10.1046/j.0019-2805.2001.01241.x -
The Journal of Experimental Medicine Jun 2007CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. Uncertainties about its biological function plagued the early years... (Review)
Review
CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. Uncertainties about its biological function plagued the early years after its discovery until 1995, when it was confirmed to be an inhibitor of T cell responses. CTLA-4 has since scored in the clinic as a target for antitumor therapy and as a soluble inhibitor of autoimmunity.
Topics: Antigens, CD; Antigens, Differentiation; B7-1 Antigen; CD8-Positive T-Lymphocytes; CTLA-4 Antigen; Cell Proliferation; Humans; Immunosuppressive Agents
PubMed: 17632849
DOI: 10.1084/jem.2046fta -
Immunology Aug 1984Monoclonal antibodies and the immunoperoxidase technique were used to localize some cell surface antigens of rat lymphoid cells and cell surface differentiation antigens...
Monoclonal antibodies and the immunoperoxidase technique were used to localize some cell surface antigens of rat lymphoid cells and cell surface differentiation antigens on cryostat sections of early rat pregnancies. The W3/13 leucocyte sialoglycoprotein was detected almost constantly on trophoblast. The immunoglobulins were more associated with mother's rather than with embryo-derived tissues. We were unable to detect considerable amounts of class I and class II major histocompatibility complex-derived antigens on trophoblast and adjacent decidual cells. The Ia+ cells of the lymphocyte type were occasionally detected in the sites exhibiting presence of immunoglobulins. The Thy-1 cell surface differentiation antigen was detected on the cells producing Thy-1+ material among decidual cells. Depletion of Thy-1 was followed by the regression of decidualized tissue. The OX-2 antigen, known as minor glycoprotein of rat thymocytes, was detected on trophoblast cells and endothelia of decidual vessels, the latter exhibiting also class I major histocompatibility complex-derived antigens. The non-pregnant uterine tissues, as well as the oviduct epithelium were also investigated. The possible role of some of these antigens in the maintenance of the 'immunologically privileged' stage of trophoblast, and in the control of the rearrangement of maternal tissues surrounding the embryo, is discussed.
Topics: Animals; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Decidua; Embryo Implantation; Fallopian Tubes; Female; Lymphocytes; Pregnancy; Pregnancy, Animal; Rats; Thy-1 Antigens; Uterus
PubMed: 6146566
DOI: No ID Found -
Cellular & Molecular Immunology Feb 2004The past years have witnessed significant advance in our understanding of critical roles of T cell co-signals in B7-CD28 family molecules in regulating T cell activation... (Review)
Review
The past years have witnessed significant advance in our understanding of critical roles of T cell co-signals in B7-CD28 family molecules in regulating T cell activation and tolerance. New co-signaling molecules have been identified and their functions have been delineated. These co-signaling pathways play overlapping and distinct regulatory roles at various stages of a T cell response. By expressing in appropriate time and location, these pathways have different regulatory functions through independent receptors or on different subsets of lymphocytes. Precise understanding of these pathways will allow the development of novel approaches to treatment of human diseases such as cancer, viral infection, autoimmune diseases and transplantation rejection.
Topics: Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, T-Lymphocyte; B7-1 Antigen; B7-2 Antigen; CD28 Antigens; CTLA-4 Antigen; Humans; Inducible T-Cell Co-Stimulator Protein; Lymphocyte Activation; Receptors, Immunologic; Signal Transduction; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 16212919
DOI: No ID Found