Cryptococcal capsular glucuronoxylomannan reduces ischaemia-related neutrophil influx

• Published in: European journal of clinical investigation Vol. 34; no. 9; pp. 631 - 640
• Main Authors: Ellerbroek, P. M., Schoemaker, R. G., Van Veghel, R., Hoepelman, A. I. M., Coenjaerts, F. E. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Animals; Biological and medical sciences; Complement C5 - immunology; Coronary Vessels; Cryptococcosis - immunology; Cryptococcus; Cryptococcus neoformans; General aspects; glucuronoxylomannan; Human mycoses; Infectious diseases; inflammation; ischaemia; Ligation; Male; Medical sciences; Miscellaneous mycoses; Mycoses; Myocardial Ischemia - immunology; myocardium; neutrophils; Neutrophils - immunology; Polysaccharides - pharmacology; Rats; Rats, Wistar; Mycosis; glucuronoxylomannan; Cryptococcosis; Granulocyte; Cardiovascular disease; Inflammation; Infection; Medicine; ischaemia; Ischemia; Myocardium; Cryptococcus; Neutrophil; neutrophils
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01393.x

Background  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. Materials and methods  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. Results  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. Conclusion  Purified cryptococcal GXM has the ability to reduce neutrophil influx even outside the scope of infection.