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
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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.