Neutrophil adherence to lung epithelial cells induce interleukin-8 release.
BACKGROUND
Neutrophil recruitment to the lungs and transmigration through the pulmonary epithelium to reach the respiratory tract are characteristics of airway inflammation. Interleukin-8 (IL-8) plays a critical role in the recruitment of neutrophils to epithelial cells. We investigated the effect of neutrophil adherence to epithelial cells on cytokine secretion.


METHODS
The production of IL-8 from cultured A549 epithelial cells was assayed and neutrophil adherence assay in the presence or absence of interferon-gamma (IFN-gamma) plus tumor necrosis factor-alpha (TNF-alpha) plus interleukin-1 beta (IL-1 beta) stimulation was studied on cultured A549 epithelial cells. The role of an adhesion molecule in the modulation of neutrophil adherence was examined by pretreatment with intercellular adhesion molecule-1 (ICAM-1) blocking antibody.


RESULTS
There was an increase in IL-8 release from epithelial cells that was time-dependent and in the magnitude of neutrophil adherence to the epithelial cells. Stimulation of epithelial cells with IFN-gamma +TNF-alpha +IL-1 beta significantly increased IL-8 release and neutrophil adherence. The spontaneous or IFN-gamma +TNF-alpha +IL-1 beta-induced IL-8 release was significantly augmented after the addition of neutrophils. The inhibition of neutrophil adherence to epithelial cells by ICAM-1 blocking antibody downregulated the augmented release of IL-8 with or without IFN-gamma +TNF-alpha +IL-1 beta stimulation. Placing a membrane filter on cultured epithelial cells to prevent neutrophil adherence significantly decreased IL-8 release from epithelial cells with IFN-gamma +TNF-alpha +IL-1 beta stimulation.


CONCLUSIONS
Our results indicate that lung epithelial cells not only provide a harboring site for neutrophils to be activated, but also amplify the neutrophil sequestration in the lung by releasing IL-8. Moreover, the release of IL-8 is dependent on the adherence between neutrophils and lung epithelial cells.
Huang
C D
CD
Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C.
Huang
K H
KH
Lin
H C
HC
Wang
C H
CH
Kuo
H P
HP
D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*
D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1