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.
Sampson
A P
AP
Department of Pharmacology, Hunterian Institute, Royal College of Surgeons of England, London.
Thomas
R U
RU
Costello
J F
JF
Piper
P J
PJ
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D015289:Leukotrienes / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged
D015289:Leukotrienes; D000001:Calcimycin