Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness

Scott R. Grewe; Sai C. Chan; Jon M. Hanifin

doi:10.1016/0091-6749(82)90008-2

Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness

Scott R. Grewe, Sai C. Chan, Jon M. Hanifin

Research output: Contribution to journal › Article › peer-review

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Abstract

Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E₁. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

Original language	English (US)
Pages (from-to)	452-457
Number of pages	6
Journal	The Journal of Allergy and Clinical Immunology
Volume	70
Issue number	6
DOIs	https://doi.org/10.1016/0091-6749(82)90008-2
State	Published - Dec 1982
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness",

abstract = "Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.",

author = "Grewe, {Scott R.} and Chan, {Sai C.} and Hanifin, {Jon M.}",

note = "Funding Information: From the Department of Dermatology, Oregon Health Sciences University, Portland, Ore. Supported by National Institutes of Health grants 4-ROl Al 15557 and 5 T32 AM0 7153 and by Medical Research Foundation of Oregon Grant 28.21. Received for publication March 8, 1982. Accepted for publication July 14, 1982. Reprint requests to: Jon M. Hanifin, M.D., Oregon Health Sciences University, 3181 Sam Jackson Park Rd., Portland, OR 97201.",

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doi = "10.1016/0091-6749(82)90008-2",

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AU - Chan, Sai C.

AU - Hanifin, Jon M.

N1 - Funding Information: From the Department of Dermatology, Oregon Health Sciences University, Portland, Ore. Supported by National Institutes of Health grants 4-ROl Al 15557 and 5 T32 AM0 7153 and by Medical Research Foundation of Oregon Grant 28.21. Received for publication March 8, 1982. Accepted for publication July 14, 1982. Reprint requests to: Jon M. Hanifin, M.D., Oregon Health Sciences University, 3181 Sam Jackson Park Rd., Portland, OR 97201.

PY - 1982/12

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N2 - Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

AB - Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

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Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness

Abstract

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