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Infection and Immunity, April 2001, p. 2692-2699, Vol. 69, No. 4
Departments of
Immunology1 and
Medicine,2 National Jewish Medical and
Research Center, Denver, Colorado 80206, and Department of
Anatomy, Cell Biology, and Injury Sciences, UMDNJ-New Jersey
Medical School, Newark, New Jersey 071033
Received 15 September 2000/Returned for modification 11 October
2000/Accepted 26 December 2000
Human macrophages are hosts for Mycobacterium
tuberculosis, the causative agent of tuberculosis, which killed
approximately 1.87 million people in 1997. Human alveolar
macrophages do not express
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.4.2692-2699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Antimycobacterial Agent Based on mRNA Encoding Human
-Defensin 2 Enables Primary Macrophages To Restrict Growth of
Mycobacterium tuberculosis
- or
-defensins,
broad-spectrum antimicrobial peptides which are expressed in
macrophages from other species more resistant to infection with
M. tuberculosis. It has been previously reported that
M. tuberculosis is susceptible to killing by defensins,
which may explain the difference in resistance. Defensin peptides have been suggested as a possible therapeutic strategy for a variety of
infectious diseases, but development has been hampered by difficulties in their large-scale production. Here we report the cellular synthesis of human
-defensin 2 via highly efficient mRNA
transfection of human macrophages. This enabled
mycobactericidal and mycobacteristatic activity by the
macrophages. Although human macrophages are difficult to transfect with plasmid vectors, these studies illustrate that primary macrophages are permissive for mRNA transfection,
which enabled expression of a potentially therapeutic protein.
*
Corresponding author. Mailing address: Department of
Immunology, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1628. Fax: (303)
398-1225. E-mail: kisichk{at}njc.org.
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