Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor.
The bronchial epithelium is an important physical barrier that regulates physiological processes including leukocyte trafficking. The aim of the present study was to elucidate the mechanisms whereby the bronchial epithelium, stimulated by epidermal growth factor (EGF) as part of a response to acute or chronic injury, could activate and chemoattract human neutrophils. Subconfluent human bronchial epithelial (16HBE) cells were stimulated with EGF to mimic the in vivo events after injury. The effect of the resulting EGF-conditioned media (CM) was compared with that of basal-CM with respect to neutrophil activation and chemotaxis. Such findings were then confirmed using primary bronchial epithelial cells (PBECs) from healthy volunteers. EGF-CM from 16HBE cells caused increased expression of CD11b/CD66b and CD62L loss on neutrophils when compared with basal-CM. EGF-CM contained significant neutrophil chemotactic activity involving granulocyte-macrophage colony-stimulating factor and interleukin-8 that was potentiated by leukotriene B(4). This was dependent on neutrophil phosphatidylinositol-3-kinase activation and Akt phosphorylation, with partial regulation by phospholipase D, but not mammalian target of rapamycin. Consistent with these observations, EGF-CM derived from PBECs displayed increased chemotactic activity. The present results suggest that the enhanced chemotactic activity of the epidermal growth factor-conditioned epithelium can enhance neutrophil-mediated immunity during acute injury, while during continued injury and repair, as in chronic asthma, this could contribute to persistent neutrophilic inflammation.
Uddin
M
M
Allergy and Inflammation Research, Division of Infection, Inflammation and Repair, School of Medicine, Southampton, UK. M.Uddin@soton.ac.uk
Seumois
G
G
Lau
L C
LC
Rytila
P
P
Davies
D E
DE
Djukanovic
R
R
D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D017077:Culture Media, Conditioned; D004815:Epidermal Growth Factor / Q000276:immunology* / Q000502:physiology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000276:immunology; D015398:Signal Transduction
D017077:Culture Media, Conditioned; D004815:Epidermal Growth Factor