Abstract

The purpose of this proposal is to examine the activity of natural killer (NK) cells in the human lung. Natural killer cells are a morphologically distinct subpopulation of cells which have a variety of functions that may be pertinent to understanding cellular immune mechanisms in the lung which are directed against neoplastic disease. NK cells have been shown to: A) spontaneously kill tumor cells in vitro, B) limit the development of metastatic lesions in vivo, and C) interact with macrophages, dendritic cells and lymphocytes in ways that may regulate the development of cell mediated immunity. These observations suggest that NK cells may be important in tumor defense in the human lung. This hypothesis will be tested by purifying lymphocytes expressing NK markers from resected lung specimens. The effector, secretory and accessory cell function of pulmonary NK subsets will be studied directly. In addition, the location of pulmonary NK in the lung will be determined by immunohistological techniques. The role that pulmonary macrophages may play in regulating pulmonary NK, which may be important in vivo will also be determined. Information derived from these experiments should be valuable to understanding a possible mechanism of pulmonary defense against neoplastic disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001797-03
Application #
3082170
Study Section
(SRC)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Yarbrough Jr, W C; Wilkes, D S; Weissler, J C (1994) Inhibition of lymphokine-activated killer cells by human pulmonary macrophages: discordance between up-regulation of the beta chain (p75) of the interleukin-2 receptor on CD56+ cells and limited response to interleukin-2. Am J Respir Cell Mol Biol 10:184-91
Wilkes, D S; Weissler, J C (1994) Alloantigen-induced immunoglobulin production in human lung: differential effects of accessory cell populations on IgG synthesis. Am J Respir Cell Mol Biol 10:339-46
Wilkes, D S; Yarbrough Jr, W C; Weissler, J C (1993) Human alveolar macrophages inhibit immunoglobulin production in response to direct B cell mitogen. Am J Respir Cell Mol Biol 9:141-7
Yarbrough Jr, W C; Wilkes, D S; Weissler, J C (1991) Human alveolar macrophages inhibit receptor-mediated increases in intracellular calcium concentration in lymphocytes. Am J Respir Cell Mol Biol 5:411-5
Twigg 3rd, H L; Weissler, J C; Yoffe, B et al. (1991) Monocyte accessory cell function in patients infected with the human immunodeficiency virus. Clin Immunol Immunopathol 59:436-48
Breite, W M; Dal Nogare, A R; Yarbrough Jr, W C et al. (1990) Cytolytic human lung lymphocytes: characterization of intragranular protease content and response to interleukin-2. Am J Respir Cell Mol Biol 3:535-41
Weissler, J C; Mootz, A R (1990) Pulmonary disease in AIDS patients. Am J Med Sci 300:330-43
Nicod, L P; Lipscomb, M F; Weissler, J C et al. (1989) Mononuclear cells from human lung parenchyma support antigen-induced T lymphocyte proliferation. J Leukoc Biol 45:336-44
Twigg 3rd, H L; Lipscomb, M F; Yoffe, B et al. (1989) Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung. Am J Respir Cell Mol Biol 1:391-400
Yarbrough Jr, W C; Weissler, J C (1989) Human pulmonary natural killer (NK) cells exhibit limited lymphokine-activated killer (LAK) activity. Am J Respir Cell Mol Biol 1:305-11

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