International Immunology Advance Access originally published online on February 27, 2008
International Immunology 2008 20(4):543-553; doi:10.1093/intimm/dxn012
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evaluation of the effect of human β-defensins on neutrophil apoptosis
1 Department of Host Defense and Biochemical Research and
2 Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan
3 Seikagaku Corporation, Tokyo, Japan
4 Insititute of Ohtaka Enzyme Co., Hokkaido, Japan
Correspondence to: I. Nagaoka; E-mail: nagaokai{at}med.juntendo.ac.jp
Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. Antimicrobial human β-defensins (hBDs) not only exhibit potent bactericidal activities against Gram-negative and Gram-positive bacteria but also function as immunomodulatory molecules by inducing cytokine and chemokine production and inflammatory and immune cell activation. Neutrophil is a critical effector cell in host defense against microbial infection, and its lifespan is regulated by various pathogen- and host-derived substances. Here, to further evaluate the role of hBDs in innate immunity, we investigated the action of hBD-1 to -4 on neutrophil apoptosis. Neutrophil apoptosis was assessed using human blood neutrophils based on the morphological changes. Of note, hBD-3 most potently suppressed neutrophil apoptosis among hBD-1 to -4, accompanied with the down-regulation of truncated Bid (a pro-apoptotic protein), up-regulation of Bcl-xL (an anti-apoptotic protein) and inhibition of mitochondrial membrane potential change and caspase 3 activity. Furthermore, we revealed that neutrophils expressed CC chemokine receptor (CCR) 6, and the action of hBD-3 was completely abrogated by a neutralizing anti-CCR6 mAb. Collectively, these observations suggest that hBDs, especially hBD-3, can not only kill bacteria but also modulate (suppress) neutrophil apoptosis via the action on CCR6. Suppression of neutrophil apoptosis results in the prolongation of their lifespan and may be advantageous for the host defense against bacterial invasion.
Keywords: antimicrobial peptides, chemokine receptor, innate immunity
Transmitting editor: K. Okumura
Received 9 August 2007, accepted 23 January 2008.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. C. Galicia, M. R. Benakanakere, P. G. Stathopoulou, and D. F. Kinane Neutrophils rescue gingival epithelial cells from bacterial-induced apoptosis J. Leukoc. Biol., July 1, 2009; 86(1): 181 - 186. [Abstract] [Full Text] [PDF]
|
|