title: Myeloperoxidase deficiency enhances zymosan phagocytosis associated with up-regulation of surface expression of CD11b in mouse neutrophils.
abstract: Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO-/-) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) dramatically reduced zymosan phagocytosis. In contrast, blocking of dectin-1, toll-like receptor 2 (TLR2), or spleen tyrosine kinase (Syk) had no significant effects on phagocytosis. Western blotting analysis showed that inhibition of FAK decreased the phosphorylation of ERK1/2, indicating that ERK1/2 is a downstream regulator of FAK in neutrophils. Importantly, we found that cell surface expression of CD11b and phosphorylation of ERK1/2 was significantly higher in zymosan-stimulated MPO-/-neutrophils than in zymosan-stimulated wild-type neutrophils. Pretreatment with the MPO inhibitor 4-aminobenzoic acid hydrazide dramatically enhanced both zymosan phagocytosis and the surface expression of CD11b in wild-type neutrophils, but not in MPO-/-neutrophils. Collectively, these results strongly suggest that up-regulation of the CD11b/FAK/ERK signaling pathway due to absence of MPO enhances the zymosan phagocytic activity of mouse neutrophils.
authors.affiliation: a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Motowaki
authors.affiliation: b International College of Arts and Sciences , Yokohama City University , Yokohama , Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tamura
authors.affiliation: a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.|b International College of Arts and Sciences , Yokohama City University , Yokohama , Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Aratani
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species; D015854:Up-Regulation; D015054:Zymosan / Q000378:metabolism*
chemical_list: D018845:CD11 Antigens; D017382:Reactive Oxygen Species; D015054:Zymosan
keywords: CD11b; Phagocytosis; mitogen-activated protein kinase; myeloperoxidase; reactive oxygen species