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Antioxidants & Redox Signaling Jun 2013The hemoglobin (Hb) scavenger receptor, CD163, is a macrophage-specific protein and the upregulated expression of this receptor is one of the major changes in the... (Review)
Review
SIGNIFICANCE
The hemoglobin (Hb) scavenger receptor, CD163, is a macrophage-specific protein and the upregulated expression of this receptor is one of the major changes in the macrophage switch to alternative activated phenotypes in inflammation. Accordingly, a high CD163 expression in macrophages is a characteristic of tissues responding to inflammation. The scavenging of the oxidative and proinflammatory Hb leading to stimulation of the heme-oxygenase-1 and production of anti-inflammatory heme metabolites indicates that CD163 thereby indirectly contributes to the anti-inflammatory response.
RECENT ADVANCES
In addition to this biological role in inflammation, CD163 is a potential inflammation biomarker and a therapeutic target. The biomarker form of CD163 is the soluble plasma CD163 that arises from the increased shedding of CD163 mediated by the tumor necrosis factor-α (TNF-α) cleaving enzyme. This explains that a steadily increasing literature documents that the plasma level of soluble CD163 is increased in a large spectrum of acute and chronic inflammatory disorders. The nonshed membrane form of CD163 in macrophages constitutes a target for drugs to be directed to macrophages in inflammation. This approach has been used in an animal inflammation model to highly increase the apparent therapeutic index of anti-inflammatory glucocorticoid drug that was coupled to an anti-CD163 antibody. Furthermore, other recent animal data, which indirectly involve CD163 in macrophages, demonstrate that injections of haptoglobin attenuate Hb-induced damages after blood transfusion.
CRITICAL ISSUES AND FUTURE DIRECTIONS
The diagnostic and therapeutic properties of CD163 await further clinical studies and regulatory approval before implementation in the clinic.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Gene Expression Regulation; Haptoglobins; Hemoglobins; Humans; Inflammation; Macrophages; Receptors, Cell Surface
PubMed: 22900885
DOI: 10.1089/ars.2012.4834 -
Current Protocols in Immunology Nov 2008Macrophages are mononuclear phagocytes that are widely distributed throughout the body. These cells can contribute to development and homeostasis and participate in...
Macrophages are mononuclear phagocytes that are widely distributed throughout the body. These cells can contribute to development and homeostasis and participate in innate and adaptive immune responses. The physiology of macrophages can vary tremendously depending on the environment in which they reside and the local stimuli to which they are exposed. Macrophages are prodigious secretory cells, and in that role can promote and regulate immune responses and contribute to autoimmune pathologies. Macrophages are highly phagocytic, and in this capacity have long been considered to be essential immune effector cells. The important roles of macrophages in maintaining homeostasis and in contributing to tissue remodeling and wound healing is sometimes overlooked because of their vital role in host defense.
Topics: Animals; Antigens, CD; Biomarkers; Bone Marrow; Macrophages, Alveolar; Macrophages, Peritoneal; Mice
PubMed: 19016445
DOI: 10.1002/0471142735.im1401s83 -
Aging Feb 2020
Topics: Aging; Antigens, CD; Cardiovascular Diseases; Cardiovascular System; Cell Adhesion Molecules; Humans
PubMed: 32084008
DOI: 10.18632/aging.102868 -
Blood Feb 1994
Topics: Antibodies, Monoclonal; Antigens, CD; Databases, Factual; Humans; Leukocytes
PubMed: 8111060
DOI: No ID Found -
Blood May 2002
Topics: Antibodies, Monoclonal; Antigens, CD; Erythrocytes; Humans; Leukocytes; Receptors, Immunologic; Terminology as Topic
PubMed: 12014373
DOI: 10.1182/blood.v99.10.3877 -
FEBS Letters Jun 2009Cluster of differentiation (CD) antigens are defined when a surface molecule found on some members of a standard panel of human cells reacts with at least one novel... (Review)
Review
Cluster of differentiation (CD) antigens are defined when a surface molecule found on some members of a standard panel of human cells reacts with at least one novel antibody, and there is good accompanying molecular data. Monoclonal antibodies to surface CD antigens on leukocytes have been used for flow cytometry, and more recently to construct microarrays that capture live cells. These DotScan microarrays enable the rapid and highly parallel characterization of repertoires of CD antigens whose expression patterns may be correlated with discrete leukaemia subtypes, or used to define biomarker 'signatures' for non-hematological diseases. DotScan with fluorescence multiplexing enables profiling of CD antigens for minor subsets of cells, such as colorectal cancer cells and tumour-infiltrating lymphocytes from a surgical sample.
Topics: Antibodies, Monoclonal; Antigens, CD; Humans; Leukemia
PubMed: 19298816
DOI: 10.1016/j.febslet.2009.03.018 -
ChemMedChem Jun 2020Phosphoantigens (pAgs) are small phosphorus-containing molecules that stimulate Vγ9Vδ2 T cells with sub-nanomolar cellular potency. Recent work has revealed that these... (Review)
Review
Phosphoantigens (pAgs) are small phosphorus-containing molecules that stimulate Vγ9Vδ2 T cells with sub-nanomolar cellular potency. Recent work has revealed that these compounds work through binding to the transmembrane immunoglobulin butyrophilin 3A1 (BTN3A1) within its intracellular B30.2 domain. Engagement of BTN3A1 is critical to the formation of an immune synapse between cells that contain pAgs and the Vγ9Vδ2 T cells. This minireview summarizes the structure-activity relationships of pAgs and their implications to the mechanisms of butyrophilin 3 activation leading to Vγ9Vδ2 T cell response.
Topics: Antigens, CD; Binding Sites; Butyrophilins; Humans; Intraepithelial Lymphocytes; Ligands; Molecular Structure; Organophosphates; Protein Binding; Protein Domains; Structure-Activity Relationship
PubMed: 32453919
DOI: 10.1002/cmdc.202000198 -
International Journal of Molecular... Oct 2018Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells.... (Review)
Review
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells. CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity. Obese insulin-resistant humans with non-alcoholic fatty liver disease manifest loss of hepatic CEACAM1. In mice, deletion or functional inactivation of CEACAM1 impairs insulin clearance and compromises metabolic homeostasis which initiates the development of obesity and hepatic steatosis and fibrosis with other features of non-alcoholic steatohepatitis, and adipogenesis in white adipose depot. This is followed by inflammation and endothelial and cardiovascular dysfunctions. In obstructive and inflammatory liver diseases, soluble CEACAM1 is shed into human bile where it can serve as an indicator of liver disease. On immune cells, CEACAM1 acts as an immune checkpoint regulator, and deletion of gene in mice causes exacerbation of inflammation and hyperactivation of myeloid cells and lymphocytes. Hence, hepatic CEACAM1 resides at the central hub of immune and metabolic homeostasis in both humans and mice. This review focuses on the regulatory role of CEACAM1 in liver and biliary tract architecture in health and disease, and on its metabolic role and function as an immune checkpoint regulator of hepatic inflammation.
Topics: Animals; Antigens, CD; Carrier Proteins; Cell Adhesion Molecules; Cell Transformation, Neoplastic; Energy Metabolism; Gene Expression Regulation; Humans; Immunomodulation; Liver Diseases; Multigene Family; Protein Binding; Signal Transduction
PubMed: 30314283
DOI: 10.3390/ijms19103110 -
Seminars in Immunology Apr 2019The type I membrane protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) distinctively exhibits significant alternative splicing that... (Review)
Review
The type I membrane protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) distinctively exhibits significant alternative splicing that allows for tunable functions upon homophilic binding. CEACAM1 is highly expressed in the tumor environment and is strictly regulated on lymphocytes such that its expression is restricted to activated cells where it is now recognized to function in tolerance pathways. CEACAM1 is also an important target for microbes which have co-opted these attributes of CEACAM1 for the purposes of invading the host and evading the immune system. These properties, among others, have focused attention on CEACAM1 as a unique target for immunotherapy in autoimmunity and cancer. This review examines recent structural information derived from the characterization of CEACAM1:CEACAM1 interactions and heterophilic modes of binding especially to microbes and how this relates to CEACAM1 function. Through this, we aim to provide insights into targeting CEACAM1 for therapeutic intervention.
Topics: Animals; Antigens, CD; Cell Adhesion Molecules; Humans
PubMed: 31604530
DOI: 10.1016/j.smim.2019.101296 -
Frontiers in Immunology 2020The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and... (Review)
Review
The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and neutrophils. Both isoforms of CD83, the membrane-bound as well as its soluble form are topic of intensive research investigations. Several studies revealed that CD83 is not a typical co-stimulatory molecule, but rather plays a critical role in controlling and resolving immune responses. Moreover, CD83 is an essential factor during the differentiation of T and B lymphocytes, and the development and maintenance of tolerance. The identification of its interaction partners as well as signaling pathways have been an enigma for the last decades. Here, we report the latest data on the expression, structure, and the signaling partners of CD83. In addition, we review the regulatory functions of CD83, including its striking modulatory potential to maintain the balance between tolerance versus inflammation during homeostasis or pathologies. These immunomodulatory properties of CD83 emphasize its exceptional therapeutic potential, which has been documented in specific preclinical disease models.
Topics: Adaptive Immunity; Animals; Antigens, CD; Autoimmunity; B-Lymphocytes; Cell Differentiation; Dendritic Cells; Host Microbial Interactions; Humans; Immune Checkpoint Proteins; Immune Tolerance; Immunoglobulins; Membrane Glycoproteins; Mice; T-Lymphocytes, Regulatory; CD83 Antigen
PubMed: 32362900
DOI: 10.3389/fimmu.2020.00721