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Infection and Immunity, November 1999, p. 6084-6089, Vol. 67, No. 11
Institute for Human Gene Therapy,
Received 20 April 1999/Returned for modification 16 June
1999/Accepted 5 August 1999
Antimicrobial peptides, such as defensins or cathelicidins, are
effector substances of the innate immune system and are thought to have
antimicrobial properties that contribute to host defense. The evidence
that vertebrate antimicrobial peptides contribute to innate immunity in
vivo is based on their expression pattern and in vitro activity against
microorganisms. The goal of this study was to investigate whether the
overexpression of an antimicrobial peptide results in augmented
protection against bacterial infection. C57BL/6 mice were given an
adenovirus vector containing the cDNA for LL-37/hCAP-18, a human
cathelicidin antimicrobial peptide. Mice treated with intratracheal
LL-37/hCAP-18 vector had a lower bacterial load and a smaller
inflammatory response than did untreated mice following pulmonary
challenge with Pseudomonas aeruginosa PAO1. Systemic
expression of LL-37/hCAP-18 after intravenous injection of recombinant
adenovirus resulted in improved survival rates following intravenous
injection of lipopolysaccharide with galactosamine or Escherichia
coli CP9. In conclusion, the data demonstrate that expression of
an antimicrobial peptide by gene transfer results in augmentation of
the innate immune response, providing support for the hypothesis that
vertebrate antimicrobial peptides protect against microorganisms in vivo.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Augmentation of Innate Host Defense by Expression
of a Cathelicidin Antimicrobial Peptide
*
Corresponding author. Mailing address: 3601 Spruce St.,
204 Wistar Institute, Philadelphia, PA 19104-4268. Phone: (215)
898-3000. Fax: (215) 898-6588. E-mail:
wilsonjm{at}mail.med.upenn.edu.
Infection and Immunity, November 1999, p. 6084-6089, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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