Skip Navigation


JAC Advance Access originally published online on September 6, 2002
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
50/4/469    most recent
dkf160v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Niwa, M.
Right arrow Articles by Uematsu, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Niwa, M.
Right arrow Articles by Uematsu, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Journal of Antimicrobial Chemotherapy (2002) 50, 469-478
© 2002 The British Society for Antimicrobial Chemotherapy

Priming by grepafloxacin on respiratory burst of human neutrophils: its possible mechanism

Masayuki Niwa1,2,*, Yutaka Kanamori2, Koichi Hotta2, Hiroyuki Matsuno2, Osamu Kozawa2, Sadaki Fujimoto3 and Toshihiko Uematsu2

1 Medical Education Development Center, 2 Department of Pharmacology, Gifu University School of Medicine, 40-Tsukasamachi, Gifu 500-8705; 3 Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan

Received 1 May 2002; returned 7 June 2002; revised 16 June 2002; accepted 21 June 2002

Grepafloxacin is a broad-spectrum fluoroquinolone derivative that has good tissue penetration. We demonstrated that grepafloxacin showed a priming effect on neutrophil respiratory burst, triggered by either a chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (fMLP) or leukotriene B4 (LTB4), but not by the phorbol ester phorbol 12-myristate 13-acetate (PMA). The priming effect of grepafloxacin on fMLP-stimulated superoxide generation by human neutrophils correlated with the penetration of grepafloxacin into cells. Removal of extracellular grepafloxacin did not inhibit the priming effect on fMLP-stimulated superoxide generation. Furthermore, grepafloxacin induced the translocation of p47-phox and p67-phox to the membrane fraction of neutrophils, whereas tyrosine phosphorylation was hardly observed in neutrophils exposed to grepafloxacin. The priming effect of grepafloxacin on superoxide generation from neutrophils was not inhibited by treatment with pertussis toxin, a protein-tyrosine kinase inhibitor (ST-638) or a protein kinase C inhibitor (calphostin C), or chelation of extracellular calcium. Grepafloxacin did not change the fMLP receptor-binding properties. Taken together, these findings suggest that grepafloxacin evokes a priming effect on neutrophil superoxide generation intracellularly through the translocation of p47-phox and even p67-phox protein to the membrane fractions. GTP binding protein, protein-tyrosine phosphorylation and protein kinase C activation are not involved in the priming effect.

Keywords: free radicals, fluoroquinolone antimicrobial agents, grepafloxacin, human neutrophils, p47-phox

* Corresponding author: Tel: +81-58-267-2624; Fax: +81-58-267-2935; E-mail: mniwa{at}cc.gifu-u.ac.jp


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.