Up-regulation of human eosinophil leukotriene C-4 generation through contact with bronchial epithelial cells

Objective and Design: We studied the effect of contact with bronchial epith elial cells on the functional activity of human eosinophils, measured as th e production of a bronchoconstrictor lipid mediator, leukotriene C-4 (LTC4) to determine the role of cell-cell interaction in activation of airway eos inophils. Materials and Methods: Eosinophils were isolated from peripheral blood of a topic donors. Epithelial cells were obtained from the bronchi of surgically resected lung lobes and cultured to confluence on collagen-coated plates. Eosinophils were stimulated with platelet activating factor (PAF) or serum opsonized zymosan (SOZ) after incubation with or without epithelial cells. Leukotriene C-4 (LTC4) was assayed in supernatants by enzyme immunoassay. Results: Bronchial epithelial cells did not produce LTC4 in response to PAF or SOZ. Eosinophils pre-incubated in collagen-coated plates for 1 h produc ed LTC4 in response to both PAF (130 +/- 53 fmol/10(6) eosinophils at 10 mu mol/l PAF, 5 min) and SOZ (1,900 +/- 550 fmol/10(6) eosinophils at 2 mg/ml SOZ, 15 min). Eosinophils co-incubated with bronchial epithelial cells for 1 h produced significantly higher quantities of LTC4 in response to both P AF (310 +/- 94 fmol/10(6) eosinophils; P < 0.01) and SOZ (5,500 +/- 1,500 f mol/10(6) eosinophils; P < 0.001). Ligation of the common beta(2) integrin subunit (CD18) with a monoclonal antibody inhibited PAF-stimulated and augm ented SOZ-stimulated LTC4 generation by eosinophils alone but had marginal effects on the epithelium-dependent up-regulation. Conclusions: Contact with bronchial epithelial cells upregulates the respon siveness of human eosinophils, a finding that has significant implications in the pathology of asthma.