Pneumolysin induces release of matrix metalloproteinase-8 and -9 from human neutrophils

Cockeran, R., Mitchell, T. J., Feldman, C. and Anderson, R. (2009) Pneumolysin induces release of matrix metalloproteinase-8 and -9 from human neutrophils. European Respiratory Journal, 34(5), pp. 1167-1170. (doi: 10.1183/09031936.00007109)

Abstract

The research question addressed in the current study was: does the pneumococcal pore-forming toxin, pneumolysin, mobilise matrix metalloproteinase (MMP) -8 and -9 from isolated human blood neutrophils at sublytic concentrations of 5, 10 and 20 ng.mL(-1)? MMPs were measured in the supernatants of unstimulated neutrophils and of cells exposed to pneumolysin and the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLP; 0.1 mu M), individually and in combination, using ELISA procedures, and alterations in cytosolic Ca2+ concentrations were monitored using a fura-2 acetoxymethyl ester (fura-2/AM)-based spectrofluorimetric method. Treatment of neutrophils with pneumolysin alone caused dose-related release of both MMPs, whereas f-MLP caused modest increases; the combination of both activators was, however, most effective. Pneumolysin/f-MLP-activated release of the MMPs from the cells was paralleled by increases in cytosolic Ca2+. Exposure of human neutrophils to pneumolysin is accompanied by mobilisation of MMPs, which is potentiated by f-MLP. If operative in vivo, pneumolysin-mediated release of MMPs from neutrophils and other cell types may contribute to the pathogenesis of severe pneumococcal disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mitchell, Professor Timothy
• Authors: Cockeran, R., Mitchell, T. J., Feldman, C., and Anderson, R.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: European Respiratory Journal
• ISSN: 0903-1936
• Published Online: 01 January 2009