Myeloperoxidase-catalyzed chlorination of histamine by stimulated neutrophils

Edwin Thomas, M. M. Jefferson, D. B. Learn, C. C. King, M. K. Dabbous

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To investigate neutrophil interactions with mediators released by mast cells at sites of inflammation, stimulated neutrophils were incubated with histamine. No accumulation of chlorinated histamine derivatives was detected in the medium. Instead, histamine inhibited the formation of chloramine derivatives of other amines. Incubation with radiolabeled histamine resulted in rapid uptake of label into the cells, and most of the label could be extracted and recovered as histamine. About 3% of the label taken up was incorporated into acid-precipitable forms. Uptake depended on myeloperoxidase (MPO)-catalyzed formation of chlorinating agents. Uptake was promoted by adding MPO and blocked by the MPO inhibitor dapsone, catalase, scavengers for hypochlorous acid and chloramines, or in a low-chloride medium, but not by histamine receptor antagonists. Incubation of histamine with MPO, hydrogen peroxide, and chloride resulted in formation of mono- and dichloramine derivatives of the primary amino group. Above pH 7.0, the chloramines were primarily in uncharged, lipophilic forms as indicated by partitioning into organic solvents. Histamine is a cation at neutral pH, but chlorination eliminated the charge on the amino group and shifted the pK(a) of the imidazole ring, resulting in formation of neutral histamine-chloramines. Incubation of neutrophils or other blood cells with radiolabeled histamine-chloramines resulted in rapid uptake of label, indicating membrane permeation by the uncharged, lipid-soluble forms. Incubation with labeled histamine-dichloramine also resulted in acid-precipitable incorporation. The results indicate that MPO-catalyzed chlorination of histamine could modulate histamine activity, tissue distribution, and metabolism at sites of inflammation.

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalRedox Report
Volume5
Issue number4
DOIs
StatePublished - Jan 1 2000

Fingerprint

Chlorination
Halogenation
Histamine
Peroxidase
Neutrophils
Chloramines
Labels
Derivatives
Inflammation
Hypochlorous Acid
Histamine Receptors
Dapsone
Acids
Hydrochloric Acid
Histamine Antagonists
Tissue Distribution
Metabolism
Mast Cells
Permeation
Catalase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical

Cite this

Myeloperoxidase-catalyzed chlorination of histamine by stimulated neutrophils. / Thomas, Edwin; Jefferson, M. M.; Learn, D. B.; King, C. C.; Dabbous, M. K.

In: Redox Report, Vol. 5, No. 4, 01.01.2000, p. 191-196.

Research output: Contribution to journalArticle

Thomas, Edwin ; Jefferson, M. M. ; Learn, D. B. ; King, C. C. ; Dabbous, M. K. / Myeloperoxidase-catalyzed chlorination of histamine by stimulated neutrophils. In: Redox Report. 2000 ; Vol. 5, No. 4. pp. 191-196.
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