Immunochemical characterization of the distinct monocyte cyclic AMP-phosphodiesterase from patients with atopic dermatitis

Sai C. Chan, David Reifsnyder, Joseph A. Beavo, Jon M. Hanifin

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Background: Previous findings have suggested that the immunopathology of patients with atopic dermatitis (AD) results from altered cellular responses caused by cyclic nucleotide regulatory abnormalities. One such defect is the increased degradation of the second messenger, cyclic adenosine monophosphate (cAMP), by elevated cAMP-phosphodiesterase (PDE) activity in patients with AD. Methods: We used two monoclonal antibodies to identify the major PDE isoform in AD blood monocytes. We have also characterized the abnormal PDE activity by means of chromatofocusing and sucrose gradient centrifugation. Results: The chromatofocusing technique allowed the separation of a PDE-containing fraction (isoelectric point = 6.1) from AD monocytes but not from normal cells. This monocyte fraction accounted for most of the elevated leukocyte-PDE activity and was a cytosolic, cAMP-specific, low Michaelis constant, calcium-calmodulin-dependent enzyme, inhibited by the cAMP-PDE inhibitor, Ro 20-1724. The majority of the PDE activity in this chromatofocused fraction was immunoadsorbed by the solid-phase immobilized antibodies against calcium-calmodulin-dependent PDE. Conclusions: The increased degradation of cAMP by a unique form of PDE may cause defective regulation of intracellular functions of AD monocytes, leading to the characteristic hyperreactive immune and inflammatory events. Characterization of PDE isoenzymes from different leukocyte subpopulations may allow further expansion of cell-directed therapy for inflammatory disease.

Original languageEnglish (US)
Pages (from-to)1179-1188
Number of pages10
JournalThe Journal of Allergy and Clinical Immunology
Volume91
Issue number6
DOIs
StatePublished - Jun 1993

Keywords

  • Atopic dermatitis (AD)
  • anti-PDE monoclonal antibodies
  • chromatofocusing
  • immunoadsorption
  • mononuclear leukocytes (MNLs)
  • phosphodiesterase (PDE)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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