Enhanced leukotriene synthesis in leukocytes of atopic and asthmatic subjects.
Enhanced leukotriene synthesis in leukocytes of atopic and asthmatic subjects.
1. We have investigated the capacities of peripheral leukocytes from atopic asthmatic (AA) (n = 7), atopic non‐asthmatic (AN) (n = 7), and normal (N) (n = 7) subjects to generate the bronchoconstrictor and proinflammatory mediators leukotrienes (LTs) B4 and C4. 2. Mixed leukocyte preparations containing 61‐84% neutrophils, 2.4‐15% eosinophils, and 13‐29% mononuclear cells were incubated in vitro at 37 degrees C in the presence of calcium ionophore A23187. Synthesis of LTB4 and LTC4 was quantitated by radioimmunoassay. 3. Both in dose‐ response experiments (0‐10 microM A23187 for 5 min), and in time‐course investigations (2 microM A23187 for 0‐30 min), the mixed leukocytes of the AA and AN subjects generated on average 4‐ to 5‐fold more LTB4 and 3‐ to 5‐fold more LTC4 than the normal leukocytes (P less than 0.01 in all cases; ANOVA). 4. This enhanced LT synthesis by the AN and AA leukocytes was not due to differences in the counts of leukocyte sub‐ types, or to altered rates of LT catabolism between the subject groups. 5. LTB4 synthesis correlated significantly with LTC4 synthesis in the leukocytes of the AN and AA subjects (r = 0.81, n = 14, P less than 0.01), but not in those of the normal subjects (r = 0.19, n = 7, P greater than 0.05). 6. Our results demonstrate an up‐regulation of the leukotriene synthetic pathway in the circulating leukocytes of atopic non‐asthmatic and atopic asthmatic subjects, which may have important implications in the pathophysiology of asthma and allergy. 1992 The British Pharmacological Society
423-430
Sampson, AP
74082098-0613-46f3-8838-418c8ecd0fe0
Thomas, RU
77ff9251-07c3-4a04-991a-d5564b4ab129
Costello, JF
53748fbc-3a08-4ebb-b5db-278bac65c9b1
Piper, PJ
7d88e87e-c5a4-4dcb-b561-89340bd49778
April 1992
Sampson, AP
74082098-0613-46f3-8838-418c8ecd0fe0
Thomas, RU
77ff9251-07c3-4a04-991a-d5564b4ab129
Costello, JF
53748fbc-3a08-4ebb-b5db-278bac65c9b1
Piper, PJ
7d88e87e-c5a4-4dcb-b561-89340bd49778
Sampson, AP, Thomas, RU, Costello, JF and Piper, PJ
(1992)
Enhanced leukotriene synthesis in leukocytes of atopic and asthmatic subjects.
British Journal of Clinical Pharmacology, 33 (4), .
(doi:10.1111/j.1365-2125.1992.tb04062.x).
Abstract
1. We have investigated the capacities of peripheral leukocytes from atopic asthmatic (AA) (n = 7), atopic non‐asthmatic (AN) (n = 7), and normal (N) (n = 7) subjects to generate the bronchoconstrictor and proinflammatory mediators leukotrienes (LTs) B4 and C4. 2. Mixed leukocyte preparations containing 61‐84% neutrophils, 2.4‐15% eosinophils, and 13‐29% mononuclear cells were incubated in vitro at 37 degrees C in the presence of calcium ionophore A23187. Synthesis of LTB4 and LTC4 was quantitated by radioimmunoassay. 3. Both in dose‐ response experiments (0‐10 microM A23187 for 5 min), and in time‐course investigations (2 microM A23187 for 0‐30 min), the mixed leukocytes of the AA and AN subjects generated on average 4‐ to 5‐fold more LTB4 and 3‐ to 5‐fold more LTC4 than the normal leukocytes (P less than 0.01 in all cases; ANOVA). 4. This enhanced LT synthesis by the AN and AA leukocytes was not due to differences in the counts of leukocyte sub‐ types, or to altered rates of LT catabolism between the subject groups. 5. LTB4 synthesis correlated significantly with LTC4 synthesis in the leukocytes of the AN and AA subjects (r = 0.81, n = 14, P less than 0.01), but not in those of the normal subjects (r = 0.19, n = 7, P greater than 0.05). 6. Our results demonstrate an up‐regulation of the leukotriene synthetic pathway in the circulating leukocytes of atopic non‐asthmatic and atopic asthmatic subjects, which may have important implications in the pathophysiology of asthma and allergy. 1992 The British Pharmacological Society
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Published date: April 1992
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Local EPrints ID: 455253
URI: http://eprints.soton.ac.uk/id/eprint/455253
ISSN: 0306-5251
PURE UUID: 133aae66-6b83-4303-b054-07f009116342
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Date deposited: 15 Mar 2022 18:06
Last modified: 16 Mar 2024 15:09
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Author:
AP Sampson
Author:
RU Thomas
Author:
JF Costello
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PJ Piper
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