DOI: 10.1128/iai.69.4.2692-2699.2001. Antimycobacterial Agent Based on mRNA Encoding Human β-Defensin 2 Enables Primary Macrophages To Restrict Growth of<i>Mycobacterium tuberculosis</i>

Antimycobacterial Agent Based on mRNA Encoding Human β-Defensin 2 Enables Primary Macrophages To Restrict Growth ofMycobacterium tuberculosis

10.1128/iai.69.4.2692-2699.2001

Crossref journal-article

American Society for Microbiology

Infection and Immunity (235)

Abstract

ABSTRACTHuman macrophages are hosts forMycobacterium tuberculosis, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997. Human alveolar macrophages do not express α- or β-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection withM. tuberculosis. It has been previously reported thatM. tuberculosisis 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 β-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.

Bibliography

Kisich, K. O., Heifets, L., Higgins, M., & Diamond, G. (2001). Antimycobacterial Agent Based on mRNA Encoding Human Î²-Defensin 2 Enables Primary Macrophages To Restrict Growth ofMycobacterium tuberculosis. Infection and Immunity, 69(4), 2692â2699.

Authors 4

Kevin O. Kisich (first)
Leonid Heifets (additional)
Michael Higgins (additional)
Gill Diamond (additional)

References 34 Referenced 68

10.1093/nar/22.23.4963
10.1084/jem.184.4.1349
10.1128/IAI.67.7.3267-3275.1999
10.1128/iai.62.6.2375-2378.1994
10.1046/j.1365-2958.1999.01279.x
10.1006/clin.1998.4587
10.1073/pnas.93.10.5156
10.1073/pnas.88.9.3952
10.1128/iai.50.1.1-8.1985
10.1001/jama.282.7.677
10.1006/bmme.1996.0080
Ganz T. and R. I. Lehrer. 1995. Defensins: pharmacology and therapeutics. 66: 191–205. (10.1016/0163-7258(94)00076-F)
10.1038/43088
10.1016/0076-6879(94)36015-4
10.1016/S0021-9258(17)42145-4
10.1089/oli.1.1996.6.111
Kisich K. O. Malone R. W. Feldstein P. A. Erickson K. L. Specific inhibition of macrophage TNF-alpha expression by in vivo ribozyme treatment.J. Immunol.163199920082016 (10.4049/jimmunol.163.4.2008) / J. Immunol. / Specific inhibition of macrophage TNF-alpha expression by in vivo ribozyme treatment by Kisich K. O. (1999)
10.1016/S0965-1748(98)00101-5
10.1182/blood.V68.6.1407.1407
10.1073/pnas.86.16.6077
10.1128/iai.64.3.926-932.1996
10.1128/AAC.40.6.1482
10.1128/iai.60.11.4720-4725.1992
Ouellette A. J. IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier.Am. J. Physiol.2771999G257G261 / Am. J. Physiol. / IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier by Ouellette A. J. (1999)
10.1096/fasebj.10.11.8836041
10.1128/iai.31.2.723-731.1981
Quayle A. J. Martin Porter E. Nussbaum A. A. Wang Y.-M. Brabec C. Mok S. C. Gene expression, immunolocalization and secretion of human defensin-5 in human female genital tract.Am. J. Pathol.152199812471258 / Am. J. Pathol. / Gene expression, immunolocalization and secretion of human defensin-5 in human female genital tract by Quayle A. J. (1998)
10.1128/IAI.66.2.878-881.1998
10.1002/jlb.65.2.270
10.1165/ajrcmb.20.5.3572
Valore E. V. Ganz T. Laboratory production of antimicrobial peptides in native conformation.Methods Mol. Biol.781997115131 / Methods Mol. Biol. / Laboratory production of antimicrobial peptides in native conformation by Valore E. V. (1997)
10.1038/sj.gt.3300626
10.1006/cimm.1993.1098
10.1074/jbc.274.37.26249

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 6:01 a.m.)
Deposited	2 years, 4 months ago (April 23, 2023, 11:31 a.m.)
Indexed	5 months ago (March 27, 2025, 4:59 p.m.)
Issued	24 years, 4 months ago (April 1, 2001)
Published	24 years, 4 months ago (April 1, 2001)
Published Print	24 years, 4 months ago (April 1, 2001)

Funders 0

None

BibTeX

@article{Kisich_2001, title={Antimycobacterial Agent Based on mRNA Encoding Human β-Defensin 2 Enables Primary Macrophages To Restrict Growth ofMycobacterium tuberculosis}, volume={69}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.69.4.2692-2699.2001}, DOI={10.1128/iai.69.4.2692-2699.2001}, number={4}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Kisich, Kevin O. and Heifets, Leonid and Higgins, Michael and Diamond, Gill}, editor={Kozel, T. R.}, year={2001}, month=apr, pages={2692–2699} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        3,
        27
      ]
    ],
    "date-time": "2025-03-27T20:59:11Z",
    "timestamp": 1743109151997
  },
  "reference-count": 34,
  "publisher": "American Society for Microbiology",
  "issue": "4",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            4,
            1
          ]
        ],
        "date-time": "2001-04-01T00:00:00Z",
        "timestamp": 986083200000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        4
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title><jats:p>Human macrophages are hosts for<jats:italic>Mycobacterium tuberculosis</jats:italic>, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997. Human alveolar macrophages do not express \u03b1- or \u03b2-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection with<jats:italic>M. tuberculosis</jats:italic>. It has been previously reported that<jats:italic>M. tuberculosis</jats:italic>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 \u03b2-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.</jats:p>",
  "DOI": "10.1128/iai.69.4.2692-2699.2001",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        27
      ]
    ],
    "date-time": "2002-07-27T10:01:19Z",
    "timestamp": 1027764079000
  },
  "page": "2692-2699",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 68,
  "title": "Antimycobacterial Agent Based on mRNA Encoding Human \u03b2-Defensin 2 Enables Primary Macrophages To Restrict Growth of<i>Mycobacterium tuberculosis</i>",
  "prefix": "10.1128",
  "volume": "69",
  "author": [
    {
      "given": "Kevin O.",
      "family": "Kisich",
      "sequence": "first",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Departments of Immunology1 and"
        }
      ]
    },
    {
      "given": "Leonid",
      "family": "Heifets",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Medicine,2 National Jewish Medical and Research Center, Denver, Colorado 80206, and"
        }
      ]
    },
    {
      "given": "Michael",
      "family": "Higgins",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Medicine,2 National Jewish Medical and Research Center, Denver, Colorado 80206, and"
        }
      ]
    },
    {
      "given": "Gill",
      "family": "Diamond",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 3-->Department of Anatomy, Cell Biology, and Injury Sciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 071033"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/22.23.4963"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.184.4.1349"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.67.7.3267-3275.1999"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.62.6.2375-2378.1994"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.1999.01279.x"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/clin.1998.4587"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.10.5156"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.9.3952"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.50.1.1-8.1985"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1001/jama.282.7.677"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bmme.1996.0080"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Ganz T. and R. I. Lehrer. 1995. Defensins: pharmacology and therapeutics. 66: 191\u2013205.",
      "DOI": "10.1016/0163-7258(94)00076-F"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/43088"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0076-6879(94)36015-4"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(17)42145-4"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/oli.1.1996.6.111"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "crossref",
      "first-page": "2008",
      "DOI": "10.4049/jimmunol.163.4.2008",
      "article-title": "Specific inhibition of macrophage TNF-alpha expression by in vivo ribozyme treatment",
      "volume": "163",
      "author": "Kisich K. O.",
      "year": "1999",
      "unstructured": "Kisich K. O. Malone R. W. Feldstein P. A. Erickson K. L. Specific inhibition of macrophage TNF-alpha expression by in vivo ribozyme treatment.J. Immunol.163199920082016",
      "journal-title": "J. Immunol."
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0965-1748(98)00101-5"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V68.6.1407.1407"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.86.16.6077"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.64.3.926-932.1996"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/AAC.40.6.1482"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.60.11.4720-4725.1992"
    },
    {
      "key": "e_1_3_2_25_2",
      "first-page": "G257",
      "article-title": "IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier",
      "volume": "277",
      "author": "Ouellette A. J.",
      "year": "1999",
      "unstructured": "Ouellette A. J. IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier.Am. J. Physiol.2771999G257G261",
      "journal-title": "Am. J. Physiol."
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1096/fasebj.10.11.8836041"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/iai.31.2.723-731.1981"
    },
    {
      "key": "e_1_3_2_28_2",
      "first-page": "1247",
      "article-title": "Gene expression, immunolocalization and secretion of human defensin-5 in human female genital tract",
      "volume": "152",
      "author": "Quayle A. J.",
      "year": "1998",
      "unstructured": "Quayle A. J. Martin Porter E. Nussbaum A. A. Wang Y.-M. Brabec C. Mok S. C. Gene expression, immunolocalization and secretion of human defensin-5 in human female genital tract.Am. J. Pathol.152199812471258",
      "journal-title": "Am. J. Pathol."
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/IAI.66.2.878-881.1998"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jlb.65.2.270"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1165/ajrcmb.20.5.3572"
    },
    {
      "key": "e_1_3_2_32_2",
      "first-page": "115",
      "article-title": "Laboratory production of antimicrobial peptides in native conformation",
      "volume": "78",
      "author": "Valore E. V.",
      "year": "1997",
      "unstructured": "Valore E. V. Ganz T. Laboratory production of antimicrobial peptides in native conformation.Methods Mol. Biol.781997115131",
      "journal-title": "Methods Mol. Biol."
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.gt.3300626"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/cimm.1993.1098"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.37.26249"
    }
  ],
  "container-title": "Infection and Immunity",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/IAI.69.4.2692-2699.2001",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/IAI.69.4.2692-2699.2001",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        23
      ]
    ],
    "date-time": "2023-04-23T15:31:52Z",
    "timestamp": 1682263912000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/IAI.69.4.2692-2699.2001"
    }
  },
  "subtitle": [],
  "editor": [
    {
      "given": "T. R.",
      "family": "Kozel",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        4
      ]
    ]
  },
  "references-count": 34,
  "journal-issue": {
    "issue": "4",
    "published-print": {
      "date-parts": [
        [
          2001,
          4
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/IAI.69.4.2692-2699.2001"
  ],
  "URL": "http://dx.doi.org/10.1128/IAI.69.4.2692-2699.2001",
  "relation": {},
  "ISSN": [
    "0019-9567",
    "1098-5522"
  ],
  "subject": [],
  "container-title-short": "Infect Immun",
  "published": {
    "date-parts": [
      [
        2001,
        4
      ]
    ]
  },
  "assertion": [
    {
      "value": "2000-09-15",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2000-12-26",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-04-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}