Bactericidal activity againstPseudomonas aeruginosa is acquired by cultured human monocyte-derived macrophages after uptake of myeloperoxidase |
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Authors: | M Mathy-Hartert G Deby-Dupont P Melin M Lamy C Deby |
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Institution: | (1) Centre for the Biochemistry of Oxygen, Institut de Chimie B6, Domaine universitaire du Sart Tilman, B-4000 Liège, (Belgium);(2) Department of Anesthesiology and Intensive Care, CHU B35, Domaine universitaire du Sart Tilman, B-4000 Liège, (Belgium);(3) Medical Microbiology CHU B23, Domaine universitaire du Sart Tilman, B-4000 Liège, (Belgium) |
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Abstract: | Myeloperoxidase (MPO) is an enzyme located within polymorphonuclear neutrophils capable of producting cytotoxic oxidant species that are particularly active against bacteria with polysaccharide capsules.Pseudomonas aeruginosa (106 bacteria per 1 ml) are killed within 1 h in vitro by a MPO/H2O2/Cl– system (48 mU=132 ng of MPO). The question arose as to whether human macrophages would acquire cytotoxic activity when loaded with this enzyme. Monocytes were therefore isolated from human blood and cultured for up to ten days to induce maturation to macrophages. These cells lost endogenous MPO within five days while H2O2 production in response to stimulation by phorbol myristate acetate (10–6M) decreased to 23% within ten days. On the other hand, their capacity to take up exogenous MPO increased fourfold from day three to day ten. Human macrophages cultured from eight days (when both H2O2 production and MPO uptake were sufficient) were therefore used to study the effects of MPO uptake on cytocidal activity againstPseudomonas aeruginosa. After a 1 h MPO loading period, macrophages (5×105 cells per ml) were incubated in the presence of bacteria (0.5 to 2×106 bacteria per ml) for 2 h at 37°C. At a bacteria/macrophage ratio of 1, only 34.8±7.0% of bacteria survived (compared to killing by non-loaded macrophages), while 74.4±9.3% survived at a ratio of 4. From these results, we conclude that loading macrophages with exogenous MPO could enhance their microbicidal activity, suggesting a potentially useful therapeutic application. |
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Keywords: | Myeloperoxidase hydrogen peroxide monocytes-macrophages bactericidal activity Pseudomonas aeruginosa |
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