Reduction in leukotriene B4, generation by bronchoalveloar lavage cells in asthma
Reduction in leukotriene B4, generation by bronchoalveloar lavage cells in asthma
Background: leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypothesis was tested using bronchoalveolar lavage (BAL) to sample cells within the airways from atopic asthmatic and normal subjects, and by measuring their capacity to generate leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in response to A23187, a potent stimulus of leukotriene generation.
Methods: bronchoalveolar lavage was performed in 12 mild asymptomatic atopic asthmatic patients and 12 normal subjects. Mixed BAL cell aliquots (approximately 80% alveolar macrophages) were incubated with 0-20 μM A23187 for 10 minutes and with 4 μM A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography.
Results: mixed BAL cells from asthmatic subjects generated less LTB4 than cells from normal subjects in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng·min 10-6 cells in asthmatic subjects and 197.9 (13.9-935.6) ng·min 10-6 cells in normal subjects. There were no differences in LTC4 generation between BAL cells from asthmatic and normal subjects.
Conclusions: generation of LTB4 by BAL cells from atopic asthmatic subjects in response to A23187 was reduced. As the alveolar macrophage is the major source of LTB4 in BAL cells, these results probably reflect reduced generation of LTB4 by alveolar macrophages from asthmatic patients. This may be a consequence of monocyte migration into the lung, or altered alveolar macrophage function in asthma, or both.
Alveolar macrophage, Asthma, Leukotriene B
67-73
Restrick, L.J.
6dd6e0bd-e5c5-4f03-9b6f-760100c51045
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Piper, P.J.
65ed0e42-dac3-4f16-931d-b8fa3f97ee7c
Costello, J.F.
c4d74078-9b8b-4725-9899-5897634e7bce
1995
Restrick, L.J.
6dd6e0bd-e5c5-4f03-9b6f-760100c51045
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Piper, P.J.
65ed0e42-dac3-4f16-931d-b8fa3f97ee7c
Costello, J.F.
c4d74078-9b8b-4725-9899-5897634e7bce
Restrick, L.J., Sampson, A.P., Piper, P.J. and Costello, J.F.
(1995)
Reduction in leukotriene B4, generation by bronchoalveloar lavage cells in asthma.
Thorax, 50 (1), .
(doi:10.1136/thx.50.1.67).
Abstract
Background: leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypothesis was tested using bronchoalveolar lavage (BAL) to sample cells within the airways from atopic asthmatic and normal subjects, and by measuring their capacity to generate leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in response to A23187, a potent stimulus of leukotriene generation.
Methods: bronchoalveolar lavage was performed in 12 mild asymptomatic atopic asthmatic patients and 12 normal subjects. Mixed BAL cell aliquots (approximately 80% alveolar macrophages) were incubated with 0-20 μM A23187 for 10 minutes and with 4 μM A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography.
Results: mixed BAL cells from asthmatic subjects generated less LTB4 than cells from normal subjects in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng·min 10-6 cells in asthmatic subjects and 197.9 (13.9-935.6) ng·min 10-6 cells in normal subjects. There were no differences in LTC4 generation between BAL cells from asthmatic and normal subjects.
Conclusions: generation of LTB4 by BAL cells from atopic asthmatic subjects in response to A23187 was reduced. As the alveolar macrophage is the major source of LTB4 in BAL cells, these results probably reflect reduced generation of LTB4 by alveolar macrophages from asthmatic patients. This may be a consequence of monocyte migration into the lung, or altered alveolar macrophage function in asthma, or both.
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Published date: 1995
Keywords:
Alveolar macrophage, Asthma, Leukotriene B
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Local EPrints ID: 455215
URI: http://eprints.soton.ac.uk/id/eprint/455215
ISSN: 0040-6376
PURE UUID: ddd29cea-aab0-40dc-9ef4-7bf7061d4e99
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Date deposited: 15 Mar 2022 17:37
Last modified: 17 Mar 2024 02:43
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Author:
L.J. Restrick
Author:
P.J. Piper
Author:
J.F. Costello
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