About this Journal Submit a Manuscript Table of Contents
ISRN Microbiology
Volume 2012 (2012), Article ID 345791, 12 pages
http://dx.doi.org/10.5402/2012/345791
Review Article

Modulation of Neutrophil Apoptosis by Antimicrobial Peptides

1Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
2Atopy (Allergy) Research Center, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan
3Seikagaku Biobusiness Corporation, Tokyo 104-0033, Japan
4Institute of Ohtaka Enzyme Co., Hokkaido 047-0156, Japan

Received 1 December 2011; Accepted 11 January 2012

Academic Editors: V. Juillard, A. Mirazimi, F. Navarro-Garcia, and A. Netrusov

Copyright © 2012 Isao Nagaoka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. Human antimicrobial peptides, α-defensins (human neutrophil peptides, HNPs), human β-defensins (hBDs), and cathelicidin (LL-37) 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, we provided the evidence that HNP-1, hBD-3, and LL-37 cannot only destroy bacteria but also potently modulate (suppress) neutrophil apoptosis, accompanied with the phosphorylation of ERK-1/-2, the downregulation of tBid (an proapoptotic protein) and upregulation of Bcl- x L (an antiapoptotic protein), and the inhibition of mitochondrial membrane potential change and caspase 3 activity, possibly via the actions on the distinct receptors, the P2Y6 nucleotide receptor, the chemokine receptor CCR6, and the low-affinity formyl-peptide receptor FPRL1/the nucleotide receptor P2X7, respectively. Suppression of neutrophil apoptosis results in the prolongation of their lifespan and may be advantageous for the host defense against bacterial invasion.