title: Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway.
abstract: We investigated effects of fosfomycin (FOM) on neutrophil function, specifically the oxidative burst and adhesion molecule expression (CD11b/CD18, or MAC-1) using flow cytometry assay. Preincubation of polymorphonuclear leukocytes (PMNL) with FOM from 1 to 100 microg/ml prior to stimulation by phorbol 12-myristate 13-acetate (PMA, 2 ng/ml) significantly suppressed the oxidative burst in a concentration-dependent manner. However, FOM did not affect the oxidative burst of PMNL stimulated by a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Stimulation with PMA (2 ng/ml) caused a rapid up-regulation of CD11b surface expression on PMNL, followed by time-dependent loss of this receptor. FOM also suppressed loss of CD11b in PMNL stimulated by PMA. FOM then inhibits the PMA-induced oxidative burst and CD11b epitope loss in PMNL. The suppressive effect appears to be mediated by the protein kinase C-dependent signaling pathway.
authors.affiliation: First Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. minamina@med.kurume-u.ac.jp
authors.forename: Minako
authors.initials: M
authors.lastname: Hamada
authors.forename: Junichi
authors.initials: J
authors.lastname: Honda
authors.forename: Taro
authors.initials: T
authors.lastname: Yoshimuta
authors.forename: Takehide
authors.initials: T
authors.lastname: Fumimori
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005578:Fosfomycin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D009504:Neutrophils / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D039481:CD11b Antigen; D005578:Fosfomycin; D011493:Protein Kinase C