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Infection and Immunity, April 2001, p. 2692-2699, Vol. 69, No. 4
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 beta -Defensin 2 Enables Primary Macrophages To Restrict Growth of Mycobacterium tuberculosis

Kevin O. Kisich,1,* Leonid Heifets,2 Michael Higgins,2 and Gill Diamond3

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 alpha - or beta -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 beta -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.


Infection and Immunity, April 2001, p. 2692-2699, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2692-2699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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