Cryptococcal capsular glucuronoxylomannan reduces ischaemia-related neutrophil influx

University Medical Centre Utrecht, Utrecht, the Netherlands.
European Journal of Clinical Investigation (Impact Factor: 2.73). 10/2004; 34(9):631-40. DOI: 10.1111/j.1365-2362.2004.01393.x
Source: PubMed


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.

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    • "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). "
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