Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness

C. A. Hirshman; D. B. Leu; D. R. Austin; S. C. Chan; L. Veith; J. M. Hanifin

doi:10.1016/S0091-6749(87)80015-5

Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness

C. A. Hirshman
, D. B. Leu
, D. R. Austin
, S. C. Chan
, L. Veith
, J. M. Hanifin

Dermatology

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

12 Scopus citations

Abstract

To investigate if mononuclear leukocyte β-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.

Original language	English (US)
Pages (from-to)	46-53
Number of pages	8
Journal	The Journal of Allergy and Clinical Immunology
Volume	79
Issue number	1
DOIs	https://doi.org/10.1016/S0091-6749(87)80015-5
State	Published - Jan 1987

Funding

The BG dog model of asthma manifests the two distinct disease processes of allergy and nonspecific airway reactivity, l, 2 In 1968 Szentivanyi 3 proposed that these abnormalities resulted from decreased 13-adrenergic responsiveness. Subsequent studies of patients with asthma or atopic dermatitis demonstrated subnormal intracellular cAMP levels after 13-adrenergic stimulation of leukocytes. 4' 5 Later, the finding of similarly reduced cAMP responses after histamine and prostaglandin El stimulation suggested a broader defect of cyclic nucleotide metabolism. 68 " Those studies led to the realization that reduced cAMP levels were due to increased hydrolysis by elevated cAMP PDE activity in atopic leukocytes. 9 We then questioned whether a similar abnormality was present in the BG dog model. Because direct investigation of cellular mechanisms in lung tissues from valuable dogs are impractical on a large scale, the peripheral blood leukocyte has been studied in this model with the considerations that 13-adrenergic hy-poresponsiveness may be a generalized phenomenon From the Departmentso f Anesthesiologya nd Dermatology,O regon Health Sciences University, Portland, and the Animal Derma-tology Clinic, Portland, Ore. Supported by National Institutes of Health Grants HL 25831 and AI 18615, Received for publication Sept. 9, 1985. Accepted for publication July 5, 1986. Reprint requests: Carol A. Hirshman, M.D., Johns Hopkins Hos-pital, 600 N. Wolfe St., Baltimore, bid 21205.

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	AI 18615
National Institute of Health National Heart, Lung, and Blood Institute	R01HL025831

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/S0091-6749(87)80015-5

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title = "Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness",

abstract = "To investigate if mononuclear leukocyte β-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.",

author = "Hirshman, \{C. A.\} and Leu, \{D. B.\} and Austin, \{D. R.\} and Chan, \{S. C.\} and L. Veith and Hanifin, \{J. M.\}",

note = "Funding Information: The BG dog model of asthma manifests the two distinct disease processes of allergy and nonspecific airway reactivity, l, 2 In 1968 Szentivanyi 3 proposed that these abnormalities resulted from decreased 13-adrenergic responsiveness. Subsequent studies of patients with asthma or atopic dermatitis demonstrated subnormal intracellular cAMP levels after 13-adrenergic stimulation of leukocytes. 4' 5 Later, the finding of similarly reduced cAMP responses after histamine and prostaglandin El stimulation suggested a broader defect of cyclic nucleotide metabolism. 68 {"} Those studies led to the realization that reduced cAMP levels were due to increased hydrolysis by elevated cAMP PDE activity in atopic leukocytes. 9 We then questioned whether a similar abnormality was present in the BG dog model. Because direct investigation of cellular mechanisms in lung tissues from valuable dogs are impractical on a large scale, the peripheral blood leukocyte has been studied in this model with the considerations that 13-adrenergic hy-poresponsiveness may be a generalized phenomenon From the Departmentso f Anesthesiologya nd Dermatology,O regon Health Sciences University, Portland, and the Animal Derma-tology Clinic, Portland, Ore. Supported by National Institutes of Health Grants HL 25831 and AI 18615, Received for publication Sept. 9, 1985. Accepted for publication July 5, 1986. Reprint requests: Carol A. Hirshman, M.D., Johns Hopkins Hos-pital, 600 N. Wolfe St., Baltimore, bid 21205.",

year = "1987",

month = jan,

doi = "10.1016/S0091-6749(87)80015-5",

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AU - Hirshman, C. A.

AU - Leu, D. B.

AU - Austin, D. R.

AU - Chan, S. C.

AU - Veith, L.

AU - Hanifin, J. M.

N1 - Funding Information: The BG dog model of asthma manifests the two distinct disease processes of allergy and nonspecific airway reactivity, l, 2 In 1968 Szentivanyi 3 proposed that these abnormalities resulted from decreased 13-adrenergic responsiveness. Subsequent studies of patients with asthma or atopic dermatitis demonstrated subnormal intracellular cAMP levels after 13-adrenergic stimulation of leukocytes. 4' 5 Later, the finding of similarly reduced cAMP responses after histamine and prostaglandin El stimulation suggested a broader defect of cyclic nucleotide metabolism. 68 " Those studies led to the realization that reduced cAMP levels were due to increased hydrolysis by elevated cAMP PDE activity in atopic leukocytes. 9 We then questioned whether a similar abnormality was present in the BG dog model. Because direct investigation of cellular mechanisms in lung tissues from valuable dogs are impractical on a large scale, the peripheral blood leukocyte has been studied in this model with the considerations that 13-adrenergic hy-poresponsiveness may be a generalized phenomenon From the Departmentso f Anesthesiologya nd Dermatology,O regon Health Sciences University, Portland, and the Animal Derma-tology Clinic, Portland, Ore. Supported by National Institutes of Health Grants HL 25831 and AI 18615, Received for publication Sept. 9, 1985. Accepted for publication July 5, 1986. Reprint requests: Carol A. Hirshman, M.D., Johns Hopkins Hos-pital, 600 N. Wolfe St., Baltimore, bid 21205.

PY - 1987/1

Y1 - 1987/1

N2 - To investigate if mononuclear leukocyte β-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.

AB - To investigate if mononuclear leukocyte β-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.

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Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness

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