Calprotectin (S100A8/S100A9) and myeloperoxidase: co-regulators of formation of reactive oxygen species

• Published in: Toxins Vol. 2; no. 1; pp. 95 - 115
• Main Authors: 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
• Format: Journal Article
• Language: English; Norwegian
• Published: Switzerland MDPI AG 01.01.2010; Molecular Diversity Preservation International
• Subjects: Calgranulin B; Hydrogen Peroxide; Leukocyte L1 Antigen Complex; Neutrophils; Peroxidase; Reactive Oxygen Species - metabolism; chemiluminescence; calprotectin; albumin; S100A8/A9; myeloperoxidase; 4-hydroxy-benzoic acid; cytidine deaminase; NaOCl; polymorphonuclear neutrophils (PMN)
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins2010095

INFLAMMATORY MEDIATORS TRIGGER POLYMORPHONUCLEAR NEUTROPHILS (PMN) TO PRODUCE REACTIVE OXYGEN SPECIES (ROS: O(2) (-), H(2)O(2), ∙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 H(2)O(2) 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.