Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway
- 作者：Hamada ; Minako ; Honda ; Junichi ; Yoshimuta ; Taro ; Fumimori ; Takehide ; Okamoto ; Masaki ; Aizawa ; Hisamichi
- 关键词：Fosfomycin ; Polymorphonuclear leukocyte ; Protein kinase C ; Respiratory burst ; Macrocyte function associated antigen 1 (MAC-1)
- 刊名：International Immunopharmacology
- 出版年：2002
- 期刊代码：123_15675769
- 类别：med
- 出版时间：March, 2002
- 卷：2
- 期：4
- 页码：511-518
- 文件大小：178 K
摘要
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 μg/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.