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Exp Cell Res. 2011 Feb 15;317(4):531-8. doi: 10.1016/j.yexcr.2010.11.015. Epub 2010 Dec 3.

The human cathelicidin, LL-37, induces granzyme-mediated apoptosis in cytotoxic T lymphocytes.

Author information

1
Department of Biochemistry, School of Molecular and Systems Medicine, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. jmader@ualberta.ca

Abstract

LL-37 is a human cationic host defense peptide (antimicrobial peptide) belonging to the cathelicidin family of peptides. In this study, LL-37 was shown to kill stimulated CD8(+) T cells (Cytotoxic T lymphocytes; CTLs) via apoptosis, while having no cytotoxic effect on non-stimulated CD8(+) or CD4(+) T cells or stimulated CD4(+) T cells. Of interest, the CD8(+) cells were much more sensitive to LL-37 than many other cell types. LL-37 exposure resulted in DNA fragmentation, chromatin condensation, and the release of both granzyme A and granzyme B from intracellular granules. The importance of granzyme family members in the apoptosis of CTLs following LL-37 treatment was analyzed by using C57BL/6 lymphocytes obtained from mice that were homozygous for null mutations in the granzyme B gene, the granzyme A gene, or both granzymes A and B. Granzymes A and B were both shown to play an important role in LL-37-induced apoptosis of CTLs. Further analysis revealed that apoptosis occurred primarily through granzyme A-mediated caspase-independent apoptosis. However, caspase-dependent cell death was also observed. This suggests that LL-37 induces apoptosis in CTLs via multiple different mechanisms, initiated by the LL-37-induced leakage of granzymes from cytolytic granules. Our results imply the existence of a novel mechanism of crosstalk between the inflammatory and adaptive immune systems. Cells such as neutrophils, at the site of a tumor for example, could influence the effector, activity of CTL through the secretion of LL-37.

PMID:
21134367
DOI:
10.1016/j.yexcr.2010.11.015
[Indexed for MEDLINE]

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