Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils.

Immunology 2004 Mar;111(3):273-81

Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

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 beta-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)-alpha-treated human neutrophils. The optimal concentration required for maximal chemotactic activity was 5 micro g/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)-3alpha, 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782421PMC
http://dx.doi.org/10.1111/j.0019-2805.2004.01816.xDOI Listing
March 2004

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