Enhancement of neutrophil function by the bronchial epithelium stimulated by EGF
Uddin, M., Seumois, G., Lau, L.C., Rytila, P., Davies, D.E. and Djukanovic, R. (2008) Enhancement of neutrophil function by the bronchial epithelium stimulated by EGF. European Respiratory Journal, 31, (4), 714-724. (doi:10.1183/09031936.00144307). (PMID:18094008).
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The bronchial epithelium is an important physical barrier that also regulates physiological processes including leukocyte trafficking. We aimed 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.Sub-confluent 16HBE cells were stimulated with EGF to mimic what happens in vivo after injury. The effect of the resulting conditioned media (EGF-CM) was compared with that of basal conditioned media (basal-CM) in respect of 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 to basal-CM. EGF-CM contained significant neutrophil chemotactic activity involving GM-CSF and IL-8 that was potentiated by LTB4. This was dependent on neutrophil PI3K activation and Akt phosphorylation, with partial regulation by PLD, but not mTOR. Consistent with these observations, EGF-CM derived from PBECs displayed increased chemotactic activity.Our results suggest that the enhanced chemotactic activity of the EGF-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.
|Subjects:||Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RB Pathology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
|Date Deposited:||03 Sep 2008|
|Last Modified:||16 Jul 2012 15:43|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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