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CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency. CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stromal Cell-derived Factor-1
The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the ''CXCL12'' gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group. CXCL12 signaling has been observed in several cancers. The ''CXCL12'' gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. Structure Gene ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
WHIM Syndrome
WHIM syndrome (or Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis syndrome) is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia. Pathophysiology WHIM syndrome results from autosomal dominant mutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy-terminus truncation of the receptor of between 10 and 19 residues. The gene mutant is located on 2q21. The truncation of the receptor protein results in the inability of downregulation after stimulation. Thus, the receptor remain in an activated state. WHIM syndrome is one of only a few diseases directly and primarily caused by an aberrant chemokine, making its molecular biology important in understanding the role of cell signaling and trafficking. An association with ''GRK3'' has also been observed. Diagnosis Patients exhibit increased susceptibility to bacterial and viral infections, especially from common serotype human papilloma virus, resulting in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Plerixafor
Plerixafor (INN and USAN, trade name Mozobil) is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are then extracted from the blood and transplanted back to the patient. The drug was developed by AnorMED, which was subsequently bought by Genzyme. Medical uses Peripheral blood stem cell mobilization, which is important as a source of hematopoietic stem cells for transplantation, is generally performed using granulocyte colony-stimulating factor (G-CSF), but is ineffective in around 15 to 20% of patients. Combination of G-CSF with plerixafor increases the percentage of persons that respond to the therapy and produce enough stem cells for transplantation. The drug is approved for patients with lymphoma and multiple myeloma. Phase 2 clinical trials started in 2021 exploring the combination of plerixafor and MGTA-145, a CXCL2 ligand. Contraindications Pregnancy and lactation Studies in pregnant animals have shown ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CXC Chemokine Receptor
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6. CXCR1 and CXCR2 CXCR1 and CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as interleukin-8) and CXCL6 can both bind CXCR1 in humans, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2. They are both expressed on the surface of neutrophils in mammals. CXCR3 CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes B_cell.html"_;"title="ome_B_cell">ome_B_cells_(B_lymphocytes) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HIV Tropism
HIV tropism refers to the cell type in which the human immunodeficiency virus (HIV) infects and replicates. HIV tropism of a patient's virus is measured by the Trofile assay. HIV can infect a variety of cells such as CD4+ helper T-cells and macrophages that express the CD4 molecule on their surface. HIV-1 entry to macrophages and T helper cells is mediated not only through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells but also with its chemokine coreceptors. Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages and CD4+ T-cells. These strains are now called R5 viruses. The normal ligands for this receptor—RANTES, macrophage inflammatory protein (MIP)-1β and MIP-1α—are able to suppress HIV-1 infection ''in vitro''. This CCR5 coreceptor is used by almost all primary HIV-1 isolates regardless of viral gene ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hematopoietic Stem Cell
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm. Haematopoiesis is the process by which all mature blood cells are produced. It must balance enormous production needs (the average person produces more than 500 billion blood cells every day) with the need to regulate the number of each blood cell type in the circulation. In vertebrates, the vast majority of hematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells that are multipotent and capable of extensive se ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers. Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8-10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. These proteins have historically been known under several other names including the ''SIS family of cytokines'', ''SIG family of cytokines'', ''SCY family of cytokines'', ''Platelet factor-4 superfamily'' or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Macrophage Migration Inhibitory Factor
Macrophage migration inhibitory factor (MIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the ''MIF'' gene. MIF is an important regulator of innate immunity. The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT). CD74 is a surface receptor for MIF. Bacterial antigens stimulate white blood cells to release MIF into the blood stream. The circulating MIF binds to CD74 on other immune cells to trigger an acute immune response. Hence, MIF is classified as an inflammatory cytokine. Furthermore, glucocorticoids also stimulate white blood cells to release MIF and hence MIF partially counteracts the inhibitory effects that glucocorticoids have on the immune system. Finally trauma activates the anterior pituitary gland to release MIF. Structure Macrophage migration inhibitory factor assembles into a trimer c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bone Marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow. Human marrow produces approximately 500 billion blood cells per day, which join the systemic circulation via permeable vasculature sinusoids within the medullary cavity. All types of hematopoietic cells, including both myeloid and lymphoid lineages, are created in bone marrow; however, lymphoid cells must migrate to other lymphoid organs (e.g. thymus) in order to complete maturation. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peripheral Blood Stem Cells
Peripheral blood stem cell transplantation (PBSCT), also called "Peripheral stem cell support", is a method of replacing blood-forming stem cells. Stem cells can be destroyed through cancer treatments such as chemotherapy or radiation, as well as any blood-related diseases, such as leukemia, lymphoma, neuroblastoma and multiple myeloma. PBSCT is now a much more common procedure than its bone marrow harvest equivalent due to the ease and less invasive nature of the procedure. Studies suggest that PBSCT has a better outcome in terms of the number of hematopoietic stem cell ( CD34+ cells) yield. Immature hematopoietic stem cells in the circulating blood that are similar to those in the bone marrow are collected by apheresis from a donor (PBSC collection). The product is then administered intravenously to the patient after treatment. The administered hematopoietic stem cells then migrate to the recipient's bone marrow, through a process known as stem cell homing, where the transplante ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Damage Associated Molecular Pattern
Damage-associated molecular patterns (DAMPs) are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen. They are also known as danger-associated molecular patterns, danger signals, and alarmin because they serve as a warning sign for the organism to alert it of any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from trauma or pathogen. Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern-recognition receptor. Inflammation is a key aspect of the innate immune response because it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process. As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell, which once rele ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Dimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", '' di-'' + '' -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins. A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein-coupled cannabinoid receptors have the ability to form both homo- and heterodimers with several ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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