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

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 mM), 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.

Matrix Metalloproteinases Vary with Airway Microbiota Composition and Lung Function in Non–Cystic Fibrosis Bronchiectasis

“…MMP-8, MMP-9, and TIMP-1 are synthesized by neutrophils and stored in secondary granules, as well as produced by other cell types (22,39). Indeed, we found positive correlations between MMP-8 and MMP-9 (but not TIMP-1) levels with sputum neutrophil %, which supports literature reports that neutrophils are the primary cellular source of MMP-8 and MMP-9 in bronchiectasis (31).…”

Recognition of Streptococcus pneumoniae and Muramyl Dipeptide by NOD2 Results in Potent Induction of MMP-9, Which Can Be Controlled by Lipopolysaccharide Stimulation

“…The induction of MMP-9 by Gram-positive bacteria has been described in the literature (6,10,11). The two Gram-negative bacteria studied here did not induce high levels of MMP-9.…”

Host Response and Bacterial Virulence Factor Expression in Pseudomonas aeruginosa and Streptococcus pneumoniae Corneal Ulcers

“…Pneumolysin is released as a monomer, but intercalates into the membrane and assembles into large multimeric rings, which form pores in the cholesterol containing host cell membrane [30]. Pneumolysin also increases neutrophil degranulation and release of elastase and matrix metalloproteinases, which contribute to tissue damage in infected lungs [31], [32], and it is likely that a similar mechanism occurs in neutrophils in S. pneumoniae infected corneas. Also, in animal models of corneal infection, pneumolysin deficient mutants caused less severe keratitis than the parent strain, and exhibit less cytotoxicity to corneal epithelial cells [15], [16].…”