Up-regulation of human eosinophil leukotriene C4 generation through contact with bronchial epithelial cells.
OBJECTIVE
We studied the effect of contact with bronchial epithelial cells on the functional activity of human eosinophils, measured as the production of a bronchoconstrictor lipid mediator, leukotriene C4 (LTC4) to determine the role of cell-cell interaction in activation of airway eosinophils.


METHODS
Eosinophils were isolated from peripheral blood of atopic 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 C4 (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 produced LTC4 in response to both PAF (130 +/- 53 fmol/10(6) eosinophils at 10 micromol/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 PAF (310 +/- 94 fmol/10(6) eosinophils; P<0.01) and SOZ (5,500 +/- 1,500 fmol/10(6) eosinophils; P<0.001). Ligation of the common beta2 integrin subunit (CD18) with a monoclonal antibody inhibited PAF-stimulated and augmented SOZ-stimulated LTC4 generation by eosinophils alone but had marginal effects on the epithelium-dependent up-regulation.


CONCLUSIONS
Contact with bronchial epithelial cells up-regulates the responsiveness of human eosinophils, a finding that has significant implications in the pathology of asthma.
Dent
G
G
Medical Specialities CD152, Southampton General Hospital, United Kingdom. g.dent@soton.ac.uk
Rühlmann
E
E
Bodtke
K
K
Magnussen
H
H
Rabe
K F
KF
D001249:Asthma / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D018821:CD18 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004804:Eosinophils / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D015854:Up-Regulation / Q000187:drug effects*; D015054:Zymosan / Q000494:pharmacology
D018821:CD18 Antigens; D019012:Integrin beta1; D016023:Integrins; D017997:Leukotriene C4; D015054:Zymosan