Disease relevance of prometryn

• Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing [1].
• Pharmacology of selectin inhibitors in ischemia/reperfusion states [2].
• A critical temporal window for selectin-dependent CD4+ lymphocyte homing and initiation of late-phase inflammation in contact sensitivity [3].
• Pertussis toxin binds target cells through the carbohydrate recognition properties of two subunits, S2 and S3, which share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family [4].
• A synthetic tetrasaccharide structurally related to blood groups and selectin ligands inhibited division of astrocytes, gliomas, and neuroblastomas at micromolar concentrations [5].

Psychiatry related information on prometryn

• Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation [6].
• Elevated plasma and lung endothelial selectin levels in patients with acute respiratory distress syndrome and a history of chronic alcohol abuse [7].

High impact information on prometryn

• This initial cell contact is followed by the selectin-mediated rolling of leukocytes on the endothelial cell surface [8].
• Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation [9].
• Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23 [10].
• In contrast with the rather mild phenotypes observed in mice deficient in a single selectin gene, the doubly deficient mice present extreme leukocytosis, elevated cytokine levels, and alterations in hematopoiesis [11].
• Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling [12].

Chemical compound and disease context of prometryn

• The study of selectin involvement in ischemia/reperfusion injury has been facilitated by the development of highly specific selectin antagonists, including monoclonal antibodies, carbohydrates, small molecule inhibitors, and soluble forms of P-selectin glycoprotein ligand 1 [2].
• These results indicate that the metabolic shifts of cancer cells partly mediated by HIFs significantly enhance their adhesion to vascular endothelial cells, through both selectin- and integrin-mediated pathways, and suggest that this enhancement further facilitates hematogenous metastasis of cancers and tumor angiogenesis [13].
• Hypoxic culture of colon cancer cells induced a marked increase in expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a determinants at the cell surface, which led to a definite increase in cancer cell adhesion to endothelial E-selectin [13].
• The selectin ligand components sialyl Lewis x and sialyl Lewis a are oncodevelopmental antigens involved in progression of adenocarcinoma [14].
• In a previous study, we demonstrated that the fucose-generating FX enzyme regulates the expression of selectin ligands by B and T lymphocytes and by head and neck squamous cell carcinoma cells [15].

Biological context of prometryn

• The adhesive interaction between circulating lymphocytes and the high endothelial venules (HEV) of lymph nodes (LN) is mediated by lymphocyte L-selectin, a member of the selectin family of cell adhesion proteins [16].
• A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion [17].
• Genomic organization of the selectin family of leukocyte adhesion molecules on human and mouse chromosome 1 [18].
• In conjunction with selectin-mediated adhesion, both beta(1)- and beta(2)-integrins participate in IPC attachment to the inflamed vessel wall, whereas chemotaxis relies in part on the chemokine receptor CCR5 [19].
• The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling [20].

Anatomical context of prometryn

• Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins [21].
• The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140 [22].
• Neutrophils roll on this selectin under flow conditions similar to those found in postcapillary venules [21].
• LECAM-1 (leukocyte-endothelial cell adhesion molecule 1), the lymphocyte lectin ("selectin") homing receptor for peripheral lymph nodes (PLNs), participates in the earliest interactions of polymorphonuclear neutrophilic leukocytes (PMNs) with inflamed venules [22].
• Cultured peripheral-blood T cells can be differentiated into CLA-bearing cells, which bind both E-selectin and P-selectin, or CLA-negative cells, which bind P-selectin but do not bind E-selectin, suggesting that there is independent regulation of selectin-binding phenotypes [23].

Associations of prometryn with other chemical compounds

• Leukocyte recruitment during inflammation is achieved through a multistep paradigm that includes margination, selectin-mediated rolling, beta 2 integrin-mediated firm adhesion, emigration, and migration into the site of inflammation [24].
• More long-term leukocyte recruitment with lipopolysaccharide (4 h) was also impaired in the cremaster but not the liver microvasculature in selectin-deficient animals [25].
• These data indicate that 4-F-GlcNAc prevents CHS by inhibiting selectin ligand activity and the capacity of effector T cells to enter antigen-challenged skin without affecting the afferent phase of CHS [26].
• B-cell rolling on E-selectin required sialic acid but was independent of previously described selectin ligands [27].
• Like the related selectin endothelial leukocyte adhesion molecule-1 (ELAM-1), GMP-140 recognizes alpha(2-3)sialylated, alpha(1-3)fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells, including the sequence Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNac beta-R (sialyl Lewis x) [28].

Gene context of prometryn

• The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing [29].
• These results demonstrate a role for FucT-IV in selectin-dependent adhesion and suggest that the endothelial selectins and FucTs have distinct but overlapping functions in the immunosurveillance of the skin [30].
• Selectin-independent rolling was mediated by alpha4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1 [31].
• The selectin LAM-1 (or LECAM-1) has been described as one of the SLe(x)-presenting glycoproteins involved in neutrophil binding to ELAM-1 [32].
• IgM mAb to Lewis(x) (CD15) and sialyl Lewis(x) (CD15s), which are carbohydrate antigens related to selectin ligands, plus mAb to CD48 and CD59, could mediate rolling [33].

Analytical, diagnostic and therapeutic context of prometryn

• To examine whether the superior performance of leukocytes reflects molecular features of native ligands or cellular properties that favor selectin-mediated rolling, we coupled structurally defined selectin ligands to microspheres or K562 cells and compared their rolling on P-selectin [34].
• The purpose of the present study was to assess the efficacy of a selectin blocker (CY 1503) given as an adjunct to thrombolytic therapy to interfere with the inflammatory response after ischemia-reperfusion and subsequently reduce myocardial infarct size in the electrolytic canine model [35].
• However, when beta(2)- or selectin-null donor cells are treated with anti-alpha(4) antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found [36].
• In summary, this report provides the first evidence for communication between an inflammatory mediator and adhesion receptors at a molecular level, through selectin receptor ligation allowing permissive SOCE to occur following PAF stimulation of human neutrophils [37].
• Furthermore, the entry of selectin-ligand-positive T cells into the circulation and their accumulation in the bronchoalveolar lavage fluid indicates that these receptors may contribute to T cell recruitment [38].

References