Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Significant in vivo stimulation of granulopoiesis was induced in mice by the administration of an extract from the urine of patients with aplastic anemia (AA). Sialic acid has been identified as an important molecular component for the in vivo biological activity of this granulopoietic factor, "granulopoietin," which is distinct and different from endotoxin. Urine from patients with AA was successively fractionated by Sephadex G-50 and DEAE-cellulose chromatography. The resultant extract, which we refer to as AA urinary extract, contained approximately equal to 44 international units of erythropoietin per A unit of protein and induced 15,000 colonies of granulocyte/macrophage precursor cells (granulocyte/macrophage colony-forming units, CFU-gm) per A unit of protein with mouse bone marrow. Eight daily intraperitoneal injections of this extract in mice induced a 6.2-fold increase in peripheral blood granulocytes and a 14.6-fold increase of splenic CFU-gm, with concomitant increases in the proliferation rates of CFU-gm in both bone marrow and spleen. Pretreatment of the AA urinary extract with sialidase significantly diminished these granulopoietic effects in vivo (P less than 0.001). In contrast, both extracts (i.e., native AA and sialidase-treated AA urinary extracts) revealed high granulocyte/macrophage colony-stimulating factor activity in vitro when clonal assays were performed with mouse bone marrow. Increased in vivo and in vitro granulopoietic activities were found in the concanavalin A "break-through" fraction, indicating that these activities were due to protein(s) that did not bind to the lectin. These results reveal that this urinary extract from patients with AA is capable of inducing significant granulopoiesis in mice and that sialic acid is an important component in the maintenance of this granulopoietic effect in vivo but not in vitro.
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PMID:In vivo stimulation of murine granulopoiesis by human urinary extract from patients with aplastic anemia. 657 18

Leukocyte rolling precedes firm adhesion and emigration in inflammatory cell recruitment. Both P-selectin, an endothelial lectin that binds to sialylated O-glycans containing sialyl-Lewisx (sLex) on the granulocyte surface, and leukocyte L-selectin have been shown to mediate leukocyte rolling in vivo. Here, we investigate rolling of isolated human neutrophils (PMN), HL-60 promyelocytes, and an L-selectin-transfected cell line (300.19-L) during trauma-induced inflammation in rat mesenteric venules. HL-60 cells, which express no L-selectin but abundant sLex, rolled effectively immediately after abdominal surgery. HL-60 cell rolling was almost completely abolished by pretreatment with sialidase or monoclonal antibody (MoAb) AM-3 recognizing sLex, and was reduced by about 80% by O-sialoglycoprotein-endopeptidase (OSGP). By contrast, 300.19-L cells rolled poorly immediately after surgery but rolled well between 40 and 120 minutes after surgery. Their rolling was completely inhibited by the blocking L-selectin MoAb LAM1-3, but not by a binding control MoAb. PMN express both L-selectin and clustered, sialylated glycoproteins including P-selectin glycoprotein ligand-1 (PSGL-1). PMN showed effective rolling at all times, which was abolished by sialidase or MoAb AM-3 pretreatment during the first 30 minutes after surgery, but not later, when PMN rolling was largely L-selectin-dependent. We conclude that in trauma-induced inflammation, a two-step mechanism accounts for most of myeloid cell rolling, which initially requires O-glycans and subsequently depends on L-selectin function.
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PMID:Sialylated O-glycans and L-selectin sequentially mediate myeloid cell rolling in vivo. 754 70

Activated platelets are known to express P-selectin, a lectin-like adhesion receptor (CD62), through which they bind to sialyl Lewis X (sLex) ligands displayed on the membranes of leukocytes. To determine whether direct platelet-platelet interactions via P-selectin/sLex interactions are also possible, we have examined the ganglioside extract of human blood platelets for the presence of sLex ligands. Using the sensitive method of high-performance thin-layer chromatography (HPTLC)-immunostaining with the monoclonal antibody (mAb) CSLEX or with sialidase followed by mAbs MC480 or PM81, eight sLex bands were demonstrated at Rf 0.01, 0.03, 0.05, 0.06, 0.08, 0.10, 0.14 and 0.21 in the solvent 45:55:10 chloroform-methanol-aqueous 0.02% CaCl2. The sensitivity of all eight bands to sialidase or endoglycoceramidase confirmed that they were gangliosides. Comparison of the HPTLC mobilities and densities of platelet bands with those from five other human tissues (granulocytes, monoblasts, kidney, aortic endothelium and erythrocytes) in three different solvents revealed three major bands associated with platelets: 3 (Rf0.03), 6 (0.08) and 14 (0.21). Platelet bands were demonstrated not to have resulted from granulocyte contamination. Partial purification of platelet sLex gangliosides by high-performance liquid chromatography and their reaction with 14 oligosaccharide-specific mAbs (FH4, FH5, LM112-161, LM119-181, A5, 1B2, BR55-2, BE2, ES4, MC631, MH04, SH34, P001 and MC813-70) revealed that band 6 is a multifucosylated neolacto ganglioside and band 14 is a branched, disialo neolacto fucoganglioside. Platelet band 3 combined the features of both bands 6 and 14, and reacted differently than granulocyte band 3. These partial structures resemble gangliosides associated with adhesion in other cell systems. It is concluded that platelets express tissue-specific sLex gangliosides (sLex ligands). Thus, it is possible that platelet-platelet binding may be mediated at least partially through P-selectin/sLex interactions, especially after platelet activation.
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PMID:Detection in human blood platelets of sialyl Lewis X gangliosides, potential ligands for CD62 and other selectins. 856 44

Following activation of granulocytes, L-selectin (CD62L) is generally shed from the cellular surface, whereas Mac-1 (CD11b/CD18) expression is well known to increase. However, a number of studies in bovines and humans show that the expression of L-selectin may increase as well. This urged us to examine the possible existence of both L-selectin and Mac-1 reservoirs in bovine neutrophil and eosinophil populations through the use of flow cytometry in combination with an optimized method for cell membrane permeabilization. Augmented L-selectin and Mac-1 expression was detected in both granulocyte populations upon saponin treatment. Confocal microscopic studies indicated that both molecules exhibit a different pattern of subcellular localization. Incubation with sialidase revealed the existence of hidden L-selectin epitopes at the cell surface, while no additional Mac-1 epitopes were exposed. Platelet-activating factor stimulation decreased surface and total expression of L-selectin to the same extent in both populations, but solely affected Mac-1 surface expression on eosinophils. Moreover, cytoskeletal actin filaments and microtubules were found to be involved in the regulation of Mac-1 surface expression on bovine neutrophils and eosinophils. In marked contrast, expression of L-selectin was minimally affected by cytoskeleton perturbing agents. The present study indicates that L-selectin and Mac-1 adhesion molecules reside in distinctly located reservoirs in bovine granulocytes and can be selectively mobilized upon in vitro stimulation.
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PMID:Analysis of selective mobilization of L-selectin and Mac-1 reservoirs in bovine neutrophils and eosinophils. 1258 84

In previous studies, we have shown that the myelopoiesis dependent upon myelosupportive stroma required production of growth factors and heparan-sulphate proteoglycans, as well as generation of a negatively charged sialidase-sensitive intercellular environment between the stroma and the myeloid progenitors. In the present study, we have investigated the production, distribution and role of gangliosides in an experimental model of in vitro myelopoiesis dependent upon AFT-024 murine liver-derived stroma. We used the FDC-P1 cell line, which is dependent upon GM-CSF (granulocyte/macrophage colony-stimulating factor) for both survival and proliferation, as a reporter system to monitor bioavailability and local activity of GM-CSF. G(M3) was the major ganglioside produced by stroma, but not by myeloid cells, and it was required for optimal stroma myelosupportive function. It was released into the supernatant and selectively incorporated into the myeloid progenitor cells, where it segregated into rafts in which it co-localized with the GM-CSF-receptor alpha chain. This ganglioside was also metabolized further by myeloid cells into gangliosides of the a and b series, similar to endogenous G(M3). In these cells, G(M1) was the major ganglioside and it was segregated at the interface by stroma and myeloid cells, partially co-localizing with the GM-CSF-receptor alpha chain. We conclude that myelosupportive stroma cells produce and secrete the required growth factors, the cofactors such as heparan sulphate proteoglycans, and also supply gangliosides that are transferred from stroma to target cells, generating on the latter ones specific membrane domains with molecular complexes that include growth factor receptors.
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PMID:Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation. 1632 Nov 39