Aminobenzoic acid compounds as HOCl traps for activated neutrophils

Zhi Wu She, Dennis C. Mays, Arthur L. Sagone, W. Bruce Davis

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

This study was designed to develop traps for hypochlorous acid (HOCl) which could be used to detect HOCl in the microenvironment of activated neutrophils. Reagent HOCl was found to react with para-aminobenzoic acid (PABA) in aqueous solution to produce a predominant metabolite detectable by high performance liquid chromatography (HPLC). Mass spectroscopy and nuclear magnetic resonance identified this metabolite as the ring addition product 3- chloro PABA. The related compound para-aminosalicylic acid (PAS) was also metabolized by HOCl to 3-chloro PAS. The formation of the 3-chloro metabolite was specific for reactions involving HOCl, since several other oxidants in chloride buffer failed to produce the metabolite. Human blood neutrophils activated by phorbol myristate acetate or zymosan in the presence of PABA (or PAS) used their HOCl to produce large amounts of the 3-chloro metabolite. The formation of 3-chloro PABA was inhibited by azide, catalase, and taurine, which is consistent with the production of the metabolite by the neutrophil myeloperoxidase (MPO) pathway. The reaction of HOCl with PABA and PAS was relatively slow as shown by competitive reactions with endogenous antioxidants like taurine, methionine, and glutathione. This was confirmed in reactions involving PABA/PAS and reagent HOCl or HOCl generated by the MPO enzyme system. In these in vitro systems, glutathione and serum completely inhibited the formation of the 3-chloro metabolite. In contrast, activated neutrophils metabolized PABA/PAS to the 3-chloro metabolite even in the presence of 1% serum. These findings demonstrate that PABA and PAS are specific trapping agents for HOCl produced by neutrophils in complex biological conditions.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalFree Radical Biology and Medicine
Volume22
Issue number6
DOIs
StatePublished - Feb 28 1997

Fingerprint

Aminobenzoates
Hypochlorous Acid
4-Aminobenzoic Acid
Aminosalicylic Acid
Metabolites
Neutrophils
Taurine
Peroxidase
Glutathione
Zymosan
Azides
High performance liquid chromatography
Tetradecanoylphorbol Acetate
Serum
Oxidants
Methionine
Catalase
Chlorides
Mass Spectrometry
Buffers

Keywords

  • Antioxidant
  • Glutathione
  • Hypochlorous acid
  • Neutrophil
  • Para-aminobenzoic acid
  • Para-aminosalicylic acid
  • Trap

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Aminobenzoic acid compounds as HOCl traps for activated neutrophils. / She, Zhi Wu; Mays, Dennis C.; Sagone, Arthur L.; Davis, W. Bruce.

In: Free Radical Biology and Medicine, Vol. 22, No. 6, 28.02.1997, p. 989-998.

Research output: Contribution to journalArticle

She, Zhi Wu ; Mays, Dennis C. ; Sagone, Arthur L. ; Davis, W. Bruce. / Aminobenzoic acid compounds as HOCl traps for activated neutrophils. In: Free Radical Biology and Medicine. 1997 ; Vol. 22, No. 6. pp. 989-998.
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