title: Calprotectin (S100A8/S100A9) and myeloperoxidase: co-regulators of formation of reactive oxygen species.
abstract: 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.
authors: Norwegian Defence Research Establishment, Division for Protection, P.O.B. 25, 2027 Kjeller, Norway; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, P.O.B. 1103Blindern, N-0317, Oslo University of Oslo, Norway.
authors: Arne
authors: A
authors: Bøyum
authors: Knut Kristian
authors: KK
authors: Skrede
authors: Oddvar
authors: O
authors: Myhre
authors: Vivi-Ann
authors: VA
authors: Tennfjord
authors: Christine Gran
authors: CG
authors: Neurauter
authors: Helge
authors: H
authors: Tolleshaug
authors: Eirunn
authors: E
authors: Knudsen
authors: Per Kristian
authors: PK
authors: Opstad
authors: Magnar
authors: M
authors: Bjørås
authors: Haakon B
authors: HB
authors: Benestad
mesh_terms: D040502:Calgranulin B; D006861:Hydrogen Peroxide; D039841:Leukocyte L1 Antigen Complex; D009504:Neutrophils; D009195:Peroxidase; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D009195:Peroxidase