In vitro leukotriene (LT) C4 synthesis by blood eosinophils from atopic asthmatics: predominance of eosinophil subpopulations with high potency for LTC4 generation.

We compared the leukotriene (LT) C4 generation by the eosinophil density subpopulations isolated from the blood of asthmatics and normal subjects. Using discontinuous Percoll gradients, eosinophil subpopulations with densities of 1.075, 1.078, 1.081, 1.084, 1.087 and 1.100 g/ml were isolated from the blood of six atopic asthmatics and seven normals. In normals, most eosinophils (94%) were recovered in the density fractions (1.084, 1.087, and 1.100 g/ml). In asthmatics, the eosinophil density profile was shifted towards lower cell density: the eosinophil subsets 1.078, 1.081 and 1.084 g/ml were increased 4.5, 30.3 and 8.9-fold respectively compared to normals (p less than 0.0001); the intermediate subsets, the hypodense 1.081 and normodense 1.084 g/ml fractions being the predominant subpopulations. The ability of asthmatic eosinophil subsets 1.078 to 1.087 g/ml to release LTC4 was measured by reversed-phase HPLC, LTC4 production was highest with the normodense 1.084 g/ml eosinophil subset (149 +/- 28 pmol/10(6) eosinophils, p less than 0.01 compared to the 1.081 fraction). The eosinophils from the hypodense 1.081 g/ml fraction also released more LTC4 (112 +/- 19 pmol/10(6) eosinophils) than the 1.078 and 1.087 g/ml fractions (70 +/- 16 and 67 +/- 12 respectively, p less than 0.01). These results show that, compared to normals, blood of mild atopic asthmatics contains an elevated number of eosinophils of intermediate density which have a high capacity for LTC4 production.