Increased concentration of circulating acid glycosaminoglycans in chronic lymphocytic leukaemia and essential thrombocythaemia.
ABSTRACT To verify whether the increase in the number of circulating blood cells that synthesize glycosaminoglycans, B-lymphocytes or platelets, in proliferative disorders, may be associated with changes in the circulation of acid glycosaminoglycans, the serum and plasma concentrations of these polysaccharides have been measured in terms of their sugar components, following isolation and purification by chromatographic methods, in patients with chronic lymphocytic leukaemia or with essential thrombocythaemia and in healthy controls. In the patients, the concentrations of total circulating glycosaminoglycans and of both glucosamine-containing and galactosamine-containing serum glycosaminoglycans were significantly higher than in controls. These concentrations did not significantly correlate with the number of lymphocytes in patients with chronic lymphocytic leukaemia and of platelets in patients with essential thrombocythaemia. Analytical data suggest that excess glycosaminoglycans are mainly composed of chondroitin sulphate molecules and contain heparan sulphate structures.
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- "It circulates covalently linked to bikunin  , or as a main product of tissue catabolism or produced by blood cells, such as lymphocytes, associated with a variety of plasma proteins  . It is known that the plasma GAG association with low-density lipoproteins could affect some of their physicochemical properties  and that some physiological and pathological conditions could lead to an increase in plasma GAG levels     . Moreover, mediators of inflammation such as some cytokines and growth factors are able to modulate the size, the degree, and the pattern of sulfation, as well as the degree of epimerization of the GAG chains   . "
ABSTRACT: Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P < 0.01) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.01/2012; 2012:281284. DOI:10.1155/2012/281284
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- "Thus, we suggest that the increase in HA production observed in LBR-would be related to abnormal HA degradation due to a decrease in Hyal-2 and Hyal-3 mRNA. Since increased HA levels in serum have been reported in breast, ovarian, endometrial, bladder cancer and also in leukemia and lymphoma (Hiltunen et al. 2002; Hasselbalch et al. 1995; Hautmann et al. 2001; Burchardt et al. 2003; Calabro et al. 1998), we analyzed HA levels in mice injected with different lymphoma cells. It has been reported that serum HA levels are higher in patients with metastasis of breast cancer than in nonmetastatic patients (Delpech et al. 1990). "
ABSTRACT: Hyaluronan (HA), a component of the extracellular matrix surrounding tumors, modulates tumor progression and the immune response. Dendritic cells (DC) may tolerize or stimulate immunity against cancer. In this report, we study the association between tumor progression, HA levels and DC activation in a lymphoma model. Mice injected with the cells with highest invasive capacity (LBR-) presented increased HA in serum and lymph nodes, and decreased DC activation in infiltrated lymph nodes and liver. These findings could be related to lack of an effective antitumor immune response and suggest that serum HA levels could have a prognostic value in hematological malignancies.Immunobiology 12/2011; 217(9):842-50. DOI:10.1016/j.imbio.2011.12.006 · 3.18 Impact Factor
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- "In animals, the total amounts of GAGs in plasma (Ferlazzo et al., 1997) are similar to those measured in humans (Calatroni et al., 1992). Nevertheless, a marked increase in plasma GAG levels was observed in a wide number of diseases, especially those involving free radical damage (Friman et al., 1987; Laurent et al., 1996; Radhakrishnamurthy et al., 1998; Calabrò et al., 1998; Roughley, 2001; Plevris et al., 2000). This increase in native plasma GAGs during diseases could be a biological response in an attempt to reduce the damage produced by oxidative stress. "
ABSTRACT: Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) is an important control point in tissue remodelling. Several findings have reported a marked MMP/TIMP imbalance in a variety of in vitro models in which oxidative stress was induced. Since previous studies showed that commercial hyaluronan and chondroitin-4-sulphate are able to limit lipid peroxidation during oxidative stress, we investigated the antioxidant capacity of purified human plasma chondroitin-4-sulfate in reducing MMP and TIMP imbalance in a model of ROS-induced oxidative injury in fibroblast cultures. Purified human plasma chondroitin-4-sulfate was added to the fibroblast cultures exposed to FeSO4 plus ascorbate. We assayed cell death, MMP and TIMP mRNA expression and protein activities, DNA damage, membrane lipid peroxidation, and aconitase depletion. FeSO4 plus ascorbate produced severe death of cells and increased MMP-1, MMP-2 and MMP-9 expression and protein activities. It also caused DNA strand breaks, enhanced lipid peroxidation and decreased aconitase. TIMP-1 and TIMP-2 protein levels and mRNA expression remain unaltered. Purified human plasma C4S, at three different doses, restored the MMP/TIMP homeostasis, increased cell survival, reduced DNA damage, inhibited lipid peroxidation and limited impairment of aconitase. These results further support the hypothesis that these biomolecules possess antioxidant activity and by reducing ROS production C4S may limit cell injury produced by MMP/TIMP imbalance.Cell Biology International 02/2006; 30(1):21-30. DOI:10.1016/j.cellbi.2005.08.009 · 1.64 Impact Factor