Characterization of the interactions of the pneumolysoid, Δ6 PLY, with human neutrophils in vitro

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Authors

Cockeran, Riana
Theron, Annette J.
Mitchell, Timothy J.
Feldman, Charles
Anderson, Ronald

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Publisher

Elsevier

Abstract

The pneumolysin toxoid, Δ6 PLY, is a prototype pneumococcal protein vaccine candidate. However, its potentially detrimental residual pro-inflammatory interactions with human neutrophils are unknown. In the current study the effects of the toxoid (8–1000 ng/ml) have been compared with those of wild-type pneumolysin (WT/PLY, 8 ng/ml) on neutrophil cytosolic Ca2+ fluxes, generation of leukotriene B4 (LTB4), and release of matrix metalloproteinase-9 (MMP-9), using spectrofluorimetric, and ELISA procedures (LTB4 and MMP-9) respectively. Exposure of neutrophils to WT/PLY resulted in influx of Ca2+ and significant (P < 0.05) release of MMP-9 and generation of LTB4. However, treatment of the cells with Δ6 PLY at concentrations of up to 1000 ng/ml had only trivial effects on Ca2+ influx and no effects on either release of MMP-9 or LTB4 production. The observed absence of pro-inflammatory interactions of Δ6 PLY with neutrophils is clearly an important property of this pneumococcal protein vaccine candidate.

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Keywords

Calcium, Leukotriene B4, Matrix metalloproteinase-9, Neutrophils

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Citation

Cockeran, R, Steel, HC, Theron, AJ, Mitchell, TJ, Feldman, C & Anderson, R, Characterization of the interactions of the pneumolysoid, Δ6 PLY, with human neutrophils in vitro, Vaccine, vol. 29, no.48, pp. 8780–8782 (2011), doi: 10.1016/j.vaccine.2011.09.080