The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans interferes with the chemotaxis and transendothelial migration of neutrophils. Intravenous administration of purified GXM has been shown to reduce the influx of inflammatory cells in an animal model of bacterial infection. Here we show that isolated GXM can also interfere with neutrophil migration in a model of inflammation not related to infection. We assessed the effects of intravenous GXM on neutrophil infiltration in a rat model of myocardial ischaemia, where neutrophil infiltration has been shown to contribute to postischaemic reperfusion injury.
Rats were subjected to coronary artery ligation followed by a 3-h reperfusion period. Myeloperoxidase-activity was measured in the ischaemic tissues as a marker of neutrophil infiltration.
Intravenous administration of GXM markedly reduced the influx of neutrophils in the ischaemic myocardium as measured by a 65% reduction of tissue MPO activity. This reduction of MPO activity was clearly correlated to the serum concentration of GXM. As complement activation by GXM was minimal at the doses applied in vivo, it is unlikely that generation of chemotactic C5a in the circulation by GXM caused the observed reduction in leucocyte migration.
Purified cryptococcal GXM has the ability to reduce neutrophil influx even outside the scope of infection.
"GXM also interfered with PMN migration in response to IL-8 (Lipovsky et al., 1998a) and in agreement with this finding, it was found that the CSF leukocyte cell count was inversely correlated with the amount of GXM present in the serum (expressed as the GXM proportion in serum related to the amount present in CSF) (Lipovsky et al., 1998b). GXM also inhibited leukocyte migration into CSF in rabbit experimental models of bacterial meningitis (Lipovsky et al., 2000), as well as in some models which induce non-related neutrophil migration, such as rat model of myocardial ischaemia (Ellerbroek et al., 2004b). "
[Show abstract][Hide abstract] ABSTRACT: The capsule of the fungal pathogen Cryptococcus neoformans has been studied extensively in recent decades and a large body of information is now available to the scientific community. Well-known aspects of the capsule include its structure, antigenic properties and its function as a virulence factor. The capsule is composed primarily of two polysaccharides, glucuronoxylomannan (GXM) and galactoxylomannan (GalXM), in addition to a smaller proportion of mannoproteins (MPs). Most of the studies on the composition of the capsule have focused on GXM, which comprises more than 90% of the capsule's polysaccharide mass. It is GalXM, however, that is of particular scientific interest because of its immunological properties. The molecular structure of these polysaccharides is very complex and has not yet been fully elucidated. Both GXM and GalXM are high molecular mass polymers with the mass of GXM equaling roughly 10 times that of GalXM. Recent findings suggest, however, that the actual molecular weight might be different to what it has traditionally been thought to be. In addition to their structural roles in the polysaccharide capsule, these molecules have been associated with many deleterious effects on the immune response. Capsular components are therefore considered key virulence determinants in C. neoformans, which has motivated their use in vaccines and made them targets for monoclonal antibody treatments. In this review, we will provide an update on the current knowledge of the C. neoformans capsule, covering aspects related to its structure, synthesis and particularly, its role as a virulence factor.
[Show abstract][Hide abstract] ABSTRACT: The surface properties of monodisperse poly (N-isopropylacrylamide-co-acrylic acid) hydrogel microspheres with different sizes were studied by measuring the electrophoretic mobility of the microspheres in the solutions at pH 7.4 with the ionic strengths between 0.005 and 0.154 M at 25, 30, 33, 35, 40, and 45 °C. Poly (N-IPAAm) microspheres show positive mobility at all ionic strengths and temperatures, while poly (N-IPAAm-co-AAc) microspheres have negative mobility. Higher absolute values of electrophoretic mobility were obtained with smaller microspheres than the larger ones at each temperature. By analyzing the data with an electrokinetic theory for “soft” surfaces, it was shown that smaller microspheres have higher surface charge density than the larger ones, although the microspheres were prepared from monomer solutions with the same monomer composition. The observed size dependence of the electrophoretic mobility suggests that charged acrylic acid monomers have a tendency to be localized in the microsphere core region, whereby the surface region of microspheres becomes poor in charges, reducing the mobility of larger microspheres. On the other hand, poly (N-IPAAm) is a thermosensitive hydrogel with a phase transition temperature around 33 °C, under which it is in a swollen state and above which in shrunken state. Therefore, the surface charge density of poly (N-IPAAm-co-AAc) microspheres increased above their phase transition temperatures. Also their surfaces became harder by the shrinkage of the polymer chains at the surfaces. It was found that the smaller microspheres show higher temperature-dependent changes in their surface charge density than the larger ones.
Studies in surface science and catalysis 01/2001; 132(136):147-152. DOI:10.1016/S0167-2991(01)80295-0
[Show abstract][Hide abstract] ABSTRACT: The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans has been shown to interfere with neutrophil migration. Although several receptors have been implied to mediate this process, the structural perspectives are unknown. Here, we assess the contribution of 6-O-acetylation and xylose substitution of the (1-->3)-alpha-d-mannan backbone of GXM, the variable structural features of GXM, to the interference with neutrophil migration. We compare chemically deacetylated GXM and acetyl- or xylose-deficient GXM from genetically modified strains with wild-type GXM in their ability to inhibit the different phases of neutrophil migration. Additionally, we verify the effects of de-O-acetylation on neutrophil migration in vivo. De-O-acetylation caused a dramatic reduction of the inhibitory capacity of GXM in the in vitro assays for neutrophil chemokinesis, rolling on E-selectin and firm adhesion to endothelium. Genetic removal of xylose only marginally reduced the ability of GXM to reduce firm adhesion. In vivo, chemical deacetylation of GXM significantly reduced its ability to interfere with neutrophil recruitment in a model of myocardial ischemia (65% reduction vs a nonsignificant reduction in tissue myeloperoxidase, respectively). Our findings indicate that 6-O-acetylated mannose of GXM is a crucial motive for the inhibition of neutrophil recruitment.
The Journal of Immunology 01/2005; 173(12):7513-20. DOI:10.4049/jimmunol.173.12.7513 · 4.92 Impact Factor
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