Human β‐defensin‐2 functions as a chemotactic agent for tumour necrosis factor‐α‐treated human neutrophils

Abstract

Summary: Neutrophils are the effector cells in both innate and adaptive immunity, where they perform the functions of phagocytosis and killing of bacteria. They respond to a large number of chemoattractants, but their response to epithelial cell‐derived human β‐defensins (hBD) has not been investigated. Here we report that hBD‐2, but not hBD‐1, is a specific chemoattractant for tumour necrosis factor (TNF)‐α‐treated human neutrophils. The optimal concentration required for maximal chemotactic activity was 5 µg/ml. The effect of hBD‐2 on neutrophils was dependent on the G‐protein‐phospholipase C pathway, as demonstrated by inhibition by pertussis toxin and U‐73122. In addition, ligand‐receptor analysis indicated that the binding of hBD‐2 was markedly inhibited by macrophage inflammatory protein (MIP)‐3α, a specific and unique ligand for CCR6. Furthermore, anti‐CCR6 antibody could almost completely suppress the cell migration induced by hBD‐2, suggesting that hBD‐2 mainly utilizes CCR6 as a functional receptor. Thus, our finding that hBD‐2 is a potent chemoattractant for human neutrophils through specific receptors provides a novel mechanism by which this peptide contributes to the host defence system by recruiting neutrophils to inflammation/infection sites. This also suggests an important link between epithelial cell‐derived antibacterial peptides and neutrophils during infection or inflammation.