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Calprotectin (S100A8/S100A9) and Myeloperoxidase: Co-Regulators of Formation of Reactive Oxygen Species
Norwegian Defence Research Establishment, Division for Protection, P.O.B. 25, 2027 Kjeller, Norway
Institute of Medical Microbiology, National Hospital, 0027 Oslo, Norway
Department of Molecular Biosciences, University of Oslo, P.O. Box 1041 Blindern, NO-0316 Oslo, Norway
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, P.O.B. 1103 Blindern, N-0317, Oslo University of Oslo, Norway
Deceased on 18 October 2009
* Author to whom correspondence should be addressed.
Received: 12 December 2009; Accepted: 18 January 2010 / Published: 20 January 2010
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.