HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cockeran, R. Articles by Anderson, R. PubMed PubMed Citation Articles by Cockeran, R. Articles by Anderson, R.

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

¹ Medical Research Council, Unit for Inflammation and Immunity, Dept of Immunology, Faculty of Health Sciences, University of Pretoria, Tshwane Academic Division of the National Health Laboratory Service, Pretoria, ³ Division of Pulmonology, Dept of Medicine, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, and ² Division of Infection and Immunity, Institute for Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.

CORRESPONDENCE: R. Cockeran, Dept of Immunology; P.O. Box 2034, Pretoria 0001, South Africa. E-mail: rcockera{at}medic.up.ac.za

Keywords: Calcium, chemoattractants, matrix metalloproteinases, neutrophils, pneumolysin

Received: January 15, 2009
Accepted March 18, 2009

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 µM), 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.