Modulation of Neutrophil Apoptosis by Antimicrobial Peptides. (27th March 2012)

• Record Type: Journal Article
• Authors: Nagaoka, Isao; Suzuki, Kaori; Niyonsaba, François; Tamura, Hiroshi; Hirata, Michimasa
• Other Names: Juillard V. Academic Editor.; Mirazimi A. Academic Editor.; Navarro-Garcia F. Academic Editor.; Netrusov A. Academic Editor.
• Is Part Of: ISRN microbiology. Volume 2012(2012)
• Publication Date: 2012-03-27
• Subjects: Microbiology -- Periodicals; Microbiology; Microbiological Phenomena; Fulltext; Internet Resources; Periodicals; 579
• DOI: 10.5402/2012/345791
• Languages: English
• ISSNs: 2090-7478

Abstract

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.