Accuri C6 Flow Cytometer System

Published online before print January 22, 2010
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Yeh, M.-C.
Right arrow Articles by Ferrante, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yeh, M.-C.
Right arrow Articles by Ferrante, A.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0609399

Received for publication June 9, 2009.
Revised December 11, 2009.
Accepted for publication December 23, 2009.

Article

Regulation of neutrophil-mediated killing of Staphylococcus aureus and chemotaxis by c-jun NH2 terminal kinase

Mei-Chun Yeh *{dagger}, Violet Mukaro *{dagger}, Charles S. Hii *{dagger}, and Antonio Ferrante *{dagger}{ddagger}@

*Department of Immunopathology, Children, Youth and Women’s Health Service, North Adelaide, South Australia;{dagger}Discipline of Paediatrics, Faculty of Health Sciences, University of Adelaide, South Australia; and{ddagger}Sansom Institute, University of South Australia, Adelaide, South Australia, Australia

@ To whom correspondence should be addressed. E-mail: antonio.ferrante{at}adelaide.edu.au.


arrow
Abstract

The role of JNK in neutrophil chemotaxis and killing of microbial pathogens remains unclear. Using a recently described cell-permeable peptide inhibitor of the JNK pathway, based on the JBD of JIP-1, coupled to the protein transduction domain of HIV-TAT (TAT-JIP), in association with control peptides, we demonstrate that the JNK pathway plays a major role in regulating human neutrophil chemotaxis and killing of microbial pathogens. Serum-opsonized Staphylococcus aureus elicited JNK activation and c-jun phosphorylation. The activation of the JNK pathway and bactericidal activity were inhibited by the TAT-JIP peptide. The stimulation of oxygen radical generation by S. aureus was dependent on the JNK signaling pathway, as was the phagocytosis of serum-opsonized bacteria. Chemotaxis to activated serum complement but not random migration was inhibited by the TAT-JIP peptide. The findings demonstrate a major role for the JNK signaling pathway in neutrophil-mediated defense against microbial pathogens.

Key Words: JNK • TAT-JIP peptide • superoxide production • phagocytosis • adherence • mechanism of bactericidal activity