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Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway
Minako Hamada1, Junichi Honda, Taro Yoshimuta
1First Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. minamina@med.kurume-u.ac.jp
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.
Insights
Fosfomycin (FOM) inhibits neutrophil oxidative burst and CD11b expression triggered by PMA, but not FMLP. This effect is concentration-dependent and may involve protein kinase C signaling.
Area of Science:
- Immunology
- Pharmacology
Background:
- Neutrophils play a critical role in the immune response.
- Fosfomycin is an antibiotic with potential immunomodulatory effects.
- Understanding antibiotic effects on immune cells is crucial for optimizing treatment.
Purpose of the Study:
- To investigate the impact of fosfomycin (FOM) on neutrophil functions.
- To analyze FOM's effect on the oxidative burst and CD11b (MAC-1) expression in polymorphonuclear leukocytes (PMNL).
Main Methods:
- Flow cytometry was used to assess neutrophil function.
- PMNL were preincubated with varying concentrations of FOM.
- Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP).
Main Results:
- FOM significantly suppressed the PMA-induced oxidative burst in a concentration-dependent manner.
- FOM did not affect the oxidative burst induced by FMLP.
- FOM inhibited the PMA-induced loss of CD11b surface expression on PMNL.
Conclusions:
- Fosfomycin inhibits key neutrophil functions, specifically the PMA-induced oxidative burst and CD11b expression loss.
- The suppressive effects of FOM appear to be mediated through the protein kinase C signaling pathway.
- These findings suggest fosfomycin may modulate neutrophil activity.