Selective expansion of alveolar macrophages in vivo by adenovirus- mediated transfer of the murine granulocyte-macrophage colony-stimulating factor cDNA

Stefan Worgall, Ravi Singh, Philip L. Leopold, Robert J. Kaner, Neil R. Hackett, Norbert Topf, Malcolm A.S. Moore, Ronald Crystal

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Based on the hypothesis that genetic modification of freshly isolated alveolar macrophages (AM) with the granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA would induce AM to proliferate, this study focuses on the ability of adenoviral (Ad) vectors to transfer and efficiently express the murine (m) GM-CSF cDNA in murine AM with consequent expansion in the number of AM in vitro and in vivo. To demonstrate that an Ad vector can effectively transfer and express genes in AM, murine AM recovered by bronchoalveolar lavage from the lung of Balb/c mice were infected with an Ad vector coding for green fluorescent protein (GFP) in vitro and expressed GFP in a dose-dependent fashion. Infection of AM with an Ad vector containing an expression cassette coding for mGM-CSF led to GM-CSF expression and to AM proliferation in vitro. When AM infected with AdGFP were returned to the respiratory tract of syngeneic recipient mice, GFP-expressing cells could still be recovered by bronchoalveolar lavage 2 weeks later. In vitro infection of AM with AdmGM-CSF and subsequent transplantation of the genetically modified AM to the lungs of syngeneic recipients led to GM-CSF expression in vivo. Strikingly, the AM recovered by lavage 5 weeks after transplantation demonstrated an increased rate of proliferation, and the total number of alveolar macrophages was 1.9-fold greater than controls. Importantly, the increase in the numbers of AM was selective (ie, other inflammatory cell numbers were unchanged), and there was no modification to the lung architecture. Thus, it is feasible to genetically modify AM with Ad vectors and to use this strategy to modify the behavior of AM in vivo. Based on the importance of AM in the primary defense of the respiratory epithelial surface, this strategy may be useful in enhancing pulmonary defenses in immunodeficiency states.

Original languageEnglish
Pages (from-to)655-666
Number of pages12
JournalBlood
Volume93
Issue number2
Publication statusPublished - 15 Jan 1999
Externally publishedYes

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Alveolar Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Adenoviridae
Complementary DNA
Green Fluorescent Proteins
Lung
Bronchoalveolar Lavage
Transplantation
Aptitude
Therapeutic Irrigation
Infection
Respiratory System

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Selective expansion of alveolar macrophages in vivo by adenovirus- mediated transfer of the murine granulocyte-macrophage colony-stimulating factor cDNA. / Worgall, Stefan; Singh, Ravi; Leopold, Philip L.; Kaner, Robert J.; Hackett, Neil R.; Topf, Norbert; Moore, Malcolm A.S.; Crystal, Ronald.

In: Blood, Vol. 93, No. 2, 15.01.1999, p. 655-666.

Research output: Contribution to journalArticle

Worgall, S, Singh, R, Leopold, PL, Kaner, RJ, Hackett, NR, Topf, N, Moore, MAS & Crystal, R 1999, 'Selective expansion of alveolar macrophages in vivo by adenovirus- mediated transfer of the murine granulocyte-macrophage colony-stimulating factor cDNA', Blood, vol. 93, no. 2, pp. 655-666.
Worgall, Stefan ; Singh, Ravi ; Leopold, Philip L. ; Kaner, Robert J. ; Hackett, Neil R. ; Topf, Norbert ; Moore, Malcolm A.S. ; Crystal, Ronald. / Selective expansion of alveolar macrophages in vivo by adenovirus- mediated transfer of the murine granulocyte-macrophage colony-stimulating factor cDNA. In: Blood. 1999 ; Vol. 93, No. 2. pp. 655-666.
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