Interleukin-5 enhances eosinophil adhesion to bronchial epithelial cells.
BACKGROUND
Eosinophil-bronchial epithelial cell interactions are thought to be central to the pathogenesis of asthma, both in terms of the epithelium as a source of pro-inflammatory mediators and as a target for eosinophil-mediated damage. We have therefore investigated adhesion interactions between these two cell types.


OBJECTIVE
To determine the role of eosinophil and epithelial activation on eosinophil adhesion to bronchial epithelium and to characterize the adhesion receptors mediating eosinophil adhesion.


METHODS
Eosinophils were purified from human peripheral blood by immunomagnetic selection and adhesion to confluent cultures of the airway epithelial cell lines A549 and BEAS-2B was studied.


RESULTS
Stimulation of A549 cells with TNFalpha, IFNgamma or a combination of 50 ng/mL of TNFalpha, IFNgamma and IL-1 (cytomix) did not effect eosinophil binding despite an increase in ICAM-1 expression. Similarly stimulation of eosinophils with PAF or IL-5 had no effect on eosinophil binding to medium- or cytokine-treated A549 cells. In contrast stimulation of BEAS-2B cells with cytomix caused a significant increase in eosinophil adhesion. This was associated with an increase in expression of ICAM-1 and induced expression of VCAM-1. Treatment of eosinophils with Mn2+ and IL-5 but not eotaxin, RANTES or PAF also significantly enhanced eosinophil adhesion to medium-treated BEAS-2B cells. Using blocking mAbs we were able to demonstrate that the increased adhesion resulting from stimulation of eosinophils or BEAS-2B cells was in both cases mediated by a combination of CD18 and alpha4 integrins.


CONCLUSIONS
This study demonstrates a selective role for IL-5 in mediating integrin-dependent eosinophil adhesion to airway epithelium and once again emphasizes the importance of this cytokine in controlling eosinophil activation in diseases such as asthma.
Sanmugalingham
D
D
Division of Respiratory Medicine, Leicester University Medical School, Glenfield Hospital, Leicester, UK.
De Vries
E
E
Gauntlett
R
R
Symon
F A
FA
Bradding
P
P
Wardlaw
A J
AJ
D015703:Antigens, CD / Q000378:metabolism; D001980:Bronchi / Q000166:cytology* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000502:physiology; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; C065289:ICAM2 protein, human; D015848:Interleukin-5; D019010:Vascular Cell Adhesion Molecule-1