Abstract: Inflammatory mediators trigger polymorphonuclear neutrophils (PMN) to produce reactive oxygen species (ROS: O2-, H2O2, ∙OH). Mediated by myeloperoxidase in PMN, HOCl is formed, detectable in a chemiluminescence (CL) assay. We have shown that the abundant cytosolic PMN protein calprotectin (S100A8/A9) similarly elicits CL in response to H2O2 in a cell-free system. Myeloperoxidase and calprotectin worked synergistically. Calprotectin-induced CL increased, whereas myeloperoxidase-triggered CL decreased with pH > 7.5. Myeloperoxidase needed NaCl for CL, calprotectin did not. 4-hydroxybenzoic acid, binding ∙OH, almost abrogated calprotectin CL, but moderately increased myeloperoxidase activity. The combination of native calprotectin, or recombinant S100A8/A9 proteins, with NaOCl markedly enhanced CL. NaOCl may be the synergistic link between myeloperoxidase and calprotectin. Surprisingly- and unexplained- at higher concentration of S100A9 the stimulation vanished, suggesting a switch from pro-oxidant to anti-oxidant function. We propose that the ∙OH is predominant in ROS production by calprotectin, a function not described before.
Keywords: chemiluminescence; polymorphonuclear neutrophils (PMN); myeloperoxidase; calprotectin; S100A8/A9; NaOCl; albumin; cytidine deaminase; 4-hydroxy-benzoic acid
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
MDPI and ACS Style
Bøyum, A.; Skrede, K.K.; Myhre, O.; Tennfjord, V.-A.; Neurauter, C.G.; Tolleshaug, H.; Knudsen, E.; Opstad, P.K.; Bjørås, M.; Benestad, H.B. Calprotectin (S100A8/S100A9) and Myeloperoxidase: Co-Regulators of Formation of Reactive Oxygen Species. Toxins 2010, 2, 95-115.
Bøyum A, Skrede KK, Myhre O, Tennfjord V-A, Neurauter CG, Tolleshaug H, Knudsen E, Opstad PK, Bjørås M, Benestad HB. Calprotectin (S100A8/S100A9) and Myeloperoxidase: Co-Regulators of Formation of Reactive Oxygen Species. Toxins. 2010; 2(1):95-115.
Bøyum, Arne; Skrede, Knut Kristian; Myhre, Oddvar; Tennfjord, Vivi-Ann; Neurauter, Christine Gran; Tolleshaug, Helge; Knudsen, Eirunn; Opstad, Per Kristian; Bjørås, Magnar; Benestad, Haakon B. 2010. "Calprotectin (S100A8/S100A9) and Myeloperoxidase: Co-Regulators of Formation of Reactive Oxygen Species." Toxins 2, no. 1: 95-115.