Relationship between LTC4 generation of hypodense eosinophils and bronchial hyperreactivity in asthmatic children

In 19 asthmatic children aged 6-16 years, the degree of bronchial hyperreactivity was determined in relationship to the concentration of inhaled histamine which caused a fall of the specific conductance (sGaw) to 60% of the baseline value PC60sGaw. At the time of lung function testing, a sample of heparinized blood was obtained from each patient. Eosinophils were purified and separated into a normodense and hypodense fraction by Percoll gradient centrifugation. After in vitro stimulation by ionophore A 23187, the leukotriene C4 (LTC4) content was determined in the culture supernatants. Hypodense eosinophils of the 13 children with a histamine threshold lower than 1 mg/ml generated significantly (p less than 0.01) larger amounts of LTC4 (0.8-36.3 ng/10(6) cells) when compared to 6 children with a histamine threshold higher than 1 mg/ml (0.7-12.1 ng/10(6) cells) and 12 healthy controls (0.4-8.2 ng/10(6) cells). Preincubation of eosinophils with platelet activating factor (PAF) induced an enhanced LTC4 production, not only in hypodense cells from both asthmatic groups but also in normodense cells from patients with severe hyperresponsiveness. These results are consistent with other results which suggest an important role of eosinophils, their activation by PAF and enhanced release of spasmogenic LTC4 in the pathogenesis of asthma.