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

R Cockeran, T J Mitchell, C Feldman, R Anderson

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 microM), individually and in combination, using ELISA procedures, and alterations in cytosolic Ca(2+) 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 Ca(2+). 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.
Original languageEnglish
Pages (from-to)1167-70
Number of pages4
JournalThe European respiratory journal
Volume34
Issue number5
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Bacterial Proteins
  • Calcium
  • Chemotactic Factors
  • Cytosol
  • Enzyme-Linked Immunosorbent Assay
  • Fura-2
  • Humans
  • Inflammation
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • N-Formylmethionine Leucyl-Phenylalanine
  • Neutrophils
  • Spectrometry, Fluorescence
  • Streptolysins

Fingerprint

Dive into the research topics of 'Pneumolysin induces release of matrix metalloproteinase-8 and -9 from human neutrophils'. Together they form a unique fingerprint.

Cite this