Loss of granule myeloperoxidase during in vitro culture of human monocytes correlates with decay in antiprotozoa activity.
Level 5 - mechanism / opinion, no new human data
in vitro laboratory study on human-derived monocytes
PubMed 3034086 · doi:10.4269/ajtmh.1987.36.541
What was done
Human adherent monocytes were evaluated immediately after explantation, at 3 days, and at 10–14 days of in vitro culture. Investigators measured the magnitude of the stimulated respiratory burst (superoxide [O2-] generation) and cellular myeloperoxidase content. Microbicidal killing capacity was assessed against ingested Toxoplasma gondii and Leishmania major. To evaluate the role of peroxidase, 3-day monocytes were tested after coating organisms with eosinophil peroxidase prior to phagocytosis.
What was found
Freshly explanted monocytes generated 254 ± 38 nmol O2-/mg protein, peaked at 782 ± 45 nmol O2-/mg at 3 days, and declined to <100 nmol O2-/mg after 10–14 days. Over 85% of myeloperoxidase was lost after 3 days. Fresh monocytes killed >90% of ingested T. gondii and L. major, whereas 10–14 day monocytes killed only 12% of Toxoplasma and 33% of Leishmania. Three-day monocytes had significantly impaired antiprotozoal activity despite generating nearly 3-fold more superoxide than fresh cells; coating protozoa with eosinophil peroxidase nearly restored killing activity to fresh-cell levels.
Why it matters
The study demonstrates that the decay in cultured monocyte microbicidal efficacy against intracellular protozoa is mediated by the rapid loss of granule myeloperoxidase rather than a simple failure of superoxide production.
Limits
This is an in vitro study that may not fully reflect tissue macrophage behavior in vivo. The abstract does not provide the number of biological donors or sample size (n = ?), and exact numerical killing rates for the 3-day unaugmented monocytes were omitted.
Cited by
- context Macrophages engulf foreign particles and kill them through the Klebanoff reaction producing hydrogen peroxide and oxidants.