Mechanisms of the Macrolide-Induced Inhibition of Superoxide Generation by Neutrophils

Kohji Nozoe, Yoshitomi Aida, Takao Fukuda, Terukazu Sanui, Fusanori Nishimura

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The effect of macrolides on the superoxide (O2 ) production by neutrophils was studied. Resting neutrophils become primed by lipopolysaccharide (LPS) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), and primed neutrophils generate O2 in response to fMLP or adhesion, respectively. Both LPS-primed fMLP-stimulated O2 generation by macrolide-treated neutrophils and adhesion-stimulated O2 generation by macrolide-treated fMLP-primed neutrophils were inhibited. Macrolide inhibition of O2 generation was dependent on serum or pH. Serum could be substituted by NaHCO3. The intensity of inhibition was azithromycin = roxithromycin > clarithromycin > erythromycin, in that order. Non-antimicrobial derivatives of erythromycin, that is, EM703 and EM900, inhibited O2 generation at pH 7.4. NH4Cl abolished the activity of azithromycin (AZ) only when added to neutrophils with AZ but not after incubation with AZ, suggesting that NH4Cl prevented the influx of AZ. AZ did not affect the expression of alkaline phosphatase, CD11b, and cytochrome b558 in both resting and LPS-primed neutrophils. These results suggested that macrolides did not affect granule mobilization but inhibited O2 generation selectively.

Original languageEnglish
Pages (from-to)1039-1048
Number of pages10
JournalInflammation
Volume39
Issue number3
DOIs
Publication statusPublished - Jun 1 2016

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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