Published ahead of print on December 9, 2005, doi:10.1165/rcmb.2005-0170OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 4, April 2006, 399-409 A more recent version of this article appeared on April 1, 2006
Submitted on May 5, 2005 Apoptosis of Airway Epithelial Cells: Human Serum Sensitive Induction by the Cathelicidin LL-37Y. Elaine Lau1,1 Department of Microbiology and Immunology, University of British Columbia, Centre for Microbial Diseases and Immunity Research, Vancouver, BC, Canada, 2 Department of Microbiology and Immunology, University of British Columbia, Centre for Microbial Diseases and Immunity Research, Vancouver, BC, Canada; MRC Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom * To whom correspondence should be addressed. E-mail: bob{at}cmdr.ubc.ca.
LL-37 is a human cationic host defence peptide that is present in the specific granules of neutrophils, produced by epithelial cells from a variety of tissues, and is upregulated during inflammation, infection, and injury. It has been proposed to have a variety of antimicrobial functions, including both direct antimicrobial activity and immunomodulatory functions. Using the TUNEL assay it was demonstrated that LL-37 induced apoptosis in vitro, in the A549 human lung and 16HBE4o- human airway epithelial cell lines, and in vivo, in the murine airway. Peptide-induced apoptosis in vitro involved the activation of caspase pathways and was substantially inhibited by an inhibitor of caspase 3. Apoptosis was also inhibited by human serum, but not fetal bovine serum. Similarly human but not fetal bovine serum inhibited the cellular internalization of LL-37 and the production of IL-8 in response to LL-37 treatment of epithelial cells. The protective effects of human serum were also observed with high-density lipoproteins but not by the core peptide apolipoprotein A1, providing one possible mechanism of human serum inhibition of apoptosis. We propose that LL-37-induced apoptosis of epithelial cells at low serum tissue sites may have a protective role against bacterial infection.
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