AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 5 852-L859, Copyright © 1997 by American Physiological Society

ARTICLES

Activation of alveolar macrophages and lung host defenses using transfer of the interferon-gamma gene

D. Lei, J. R. Lancaster Jr, M. S. Joshi, S. Nelson, D. Stoltz, G. J. Bagby, G. Odom, J. E. Shellito and J. K. Kolls
Section of Pulmonary/Critical Care, Louisiana State University, New Orleans 70112, USA.

Interferon-gamma (IFN-gamma) is a critical cytokine in pulmonary host defenses against both intracellular and extracellular pathogens. To investigate whether this cytokine could be used therapeutically, we constructed an E1-deleted recombinant adenovirus encoding murine IFN-gamma. After intratracheal inoculation in rats, this vector resulted in prolonged expression of functional cytokine in vivo, as demonstrated by increased alveolar macrophage class II major histocompatibility complex expression, enhanced release of tumor necrosis factor in response to lipopolysaccharide, and enhanced host defenses against Pseudomonas aeruginosa. We postulate that this vector may be useful to study the role of exogenous IFN-gamma in a variety of pulmonary intracellular and extracellular pathogens.

This article has been cited by other articles:

				S. D. Hurst, T. Muchamuel, D. M. Gorman, J. M. Gilbert, T. Clifford, S. Kwan, S. Menon, B. Seymour, C. Jackson, T. T. Kung, et al. New IL-17 Family Members Promote Th1 or Th2 Responses in the Lung: In Vivo Function of the Novel Cytokine IL-25 J. Immunol., July 1, 2002; 169(1): 443 - 453. [Abstract] [Full Text] [PDF]

				J. C. Deng, K. Tateda, X. Zeng, and T. J. Standiford Transient Transgenic Expression of Gamma Interferon Promotes Legionella pneumophila Clearance in Immunocompetent Hosts Infect. Immun., October 1, 2001; 69(10): 6382 - 6390. [Abstract] [Full Text] [PDF]

				Z. Xing, A. Zganiacz, and M. Santosuosso Role of IL-12 in macrophage activation during intracellular infection: IL-12 and mycobacteria synergistically release TNF-{alpha} and nitric oxide from macrophages via IFN-{gamma} induction J. Leukoc. Biol., December 1, 2000; 68(6): 897 - 902. [Abstract] [Full Text]

				J. K. Kolls, S. Habetz, M. K. Shean, C. Vazquez, J. A. Brown, D. Lei, P. Schwarzenberger, P. Ye, S. Nelson, W. R. Summer, et al. IFN-{gamma} and CD8+ T Cells Restore Host Defenses Against Pneumocystis carinii in Mice Depleted of CD4+ T Cells J. Immunol., March 1, 1999; 162(5): 2890 - 2894. [Abstract] [Full Text] [PDF]

				H. L. Twigg III, B. A. Spain, D. M. Soliman, K. Knox, R. A. Sidner, C. Schnizlein-Bick, D. S. Wilkes, and G. K. Iwamoto Production of interferon-gamma by lung lymphocytes in HIV-infected individuals Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L256 - L262. [Abstract] [Full Text] [PDF]

				S. Worgall, R. Singh, P. L. Leopold, R. J. Kaner, N. R. Hackett, N. Topf, M. A.S. Moore, and R. G. Crystal Selective Expansion of Alveolar Macrophages In Vivo by Adenovirus-Mediated Transfer of the Murine Granulocyte-Macrophage Colony-Stimulating Factor cDNA Blood, January 15, 1999; 93(2): 655 - 666. [Abstract] [Full Text] [PDF]

				P. Schwarzenberger, V. La Russa, A. Miller, P. Ye, W. Huang, A. Zieske, S. Nelson, G. J. Bagby, D. Stoltz, R. L. Mynatt, et al. IL-17 Stimulates Granulopoiesis in Mice: Use of an Alternate, Novel Gene Therapy-Derived Method for In Vivo Evaluation of Cytokines J. Immunol., December 1, 1998; 161(11): 6383 - 6389. [Abstract] [Full Text] [PDF]

				M. Wu, S. Hussain, Y.-H. He, R. Pasula, P. A. Smith, and W. J. Martin II Genetically engineered macrophages expressing IFN-gamma restore alveolar immune function in scid mice PNAS, December 4, 2001; 98(25): 14589 - 14594. [Abstract] [Full Text] [PDF]