Relationship between increased cyclic ampphosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis

Jon Hanifin, Rita Lloyd, Keiji Okubo, Larry L. Guerin, Linda Fancher, Sai C. Chan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
Volume98
Issue number6 SUPPL.
StatePublished - Jun 1992

Fingerprint

Phosphoric Diester Hydrolases
Atopic Dermatitis
Adenylyl Cyclases
Leukocytes
Membranes
GTP-Binding Proteins
Monocytes
Defects
Cyclic Nucleotides
Pertussis Toxin
Labeling
Skin
Proteins
Monoclonal Antibodies
Modulation
Degradation

ASJC Scopus subject areas

  • Dermatology

Cite this

Relationship between increased cyclic ampphosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis. / Hanifin, Jon; Lloyd, Rita; Okubo, Keiji; Guerin, Larry L.; Fancher, Linda; Chan, Sai C.

In: Journal of Investigative Dermatology, Vol. 98, No. 6 SUPPL., 06.1992.

Research output: Contribution to journalArticle

@article{9fa6000a3456445494dae5595aca3bfd,
title = "Relationship between increased cyclic ampphosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis",
abstract = "Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.",
author = "Jon Hanifin and Rita Lloyd and Keiji Okubo and Guerin, {Larry L.} and Linda Fancher and Chan, {Sai C.}",
year = "1992",
month = "6",
language = "English (US)",
volume = "98",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "6 SUPPL.",

}

TY - JOUR

T1 - Relationship between increased cyclic ampphosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis

AU - Hanifin, Jon

AU - Lloyd, Rita

AU - Okubo, Keiji

AU - Guerin, Larry L.

AU - Fancher, Linda

AU - Chan, Sai C.

PY - 1992/6

Y1 - 1992/6

N2 - Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

AB - Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

UR - http://www.scopus.com/inward/record.url?scp=0026520969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026520969&partnerID=8YFLogxK

M3 - Article

VL - 98

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 6 SUPPL.

ER -