Enhancement of neutrophil function by the bronchial epithelium stimulated by EGF

M. Uddin ^1*, G. Seumois ¹, L.C. Lau ¹, P. Rytila ², D.E. Davies ¹, R. Djukanovi ¹

¹ Allergy and Inflammation Research, Division of Infection, Inflammation and Repair, School of Medicine, Level F, South Block (Mailpoint 810), Southampton General Hospital, Southampton SO16 6YD, United Kingdom
² Division of Allergy, Helsinki University Central Hospital, Helsinki, Finland

	Abstract

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.

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