Chao-Hung Lee, PhD
Professor of Pathology and Laboratory Medicine
Telephone: (317) 274-2596
FAX: (317) 278-0643
We study mechanisms of pathogenesis of Pneumocystis pneumonia (PCP). In humans, PCP is caused by Pneumocystis jirovecii. Pneumocystis is an opportunistic pathogen, and Pneumocystis pneumonia (PCP) is most commonly seen in immunocompromised individuals such as AIDS and organ transplantation patients. During PCP, alveolar macrophages are defective in phagocytosis and their number is decreased. These two defects severely disable the innate immunity against Pneumocystis infection. We found that the expression of the transcription factor GATA-2 is turned off in AMs from infected rats. We further demonstrated that this GATA-2 down-regulation correlates with the defect in phagocytosis of AMs because a normal AM becomes defective in phagocytosis when the expression of GATA-2 is knocked down. A major reason why the number of AMs is decreased during PCP is increased rate of apoptosis. We have recently shown that hat the high concentration of intracellular polyamines is a cause of this apoptosis. We further demonstrated that the expression of the protein antizyme inhibitor (AZI) is greatly increased in AMs during PCP. Since AZI enhances the uptake of exogenous polyamines and the stability of ornithine decarboxylase which is the key enzyme in polyamine synthesis, AZI over expression is a major cause of AM apoptosis during PCP. We have also found that the levels of the protein calmodulin in AMs are decreased during PCP. Since calmodulin is required for the formation of a functional inducible nitric oxide synthase, its decrease results in reduced production in nitric oxide by AMs. Recently, we found that the expression of the transcription factor PU.1 in AMs is down regulated. We hypothesize that PU.1 down regulation is anther cause of decreased phagocytic activity and number of AMs during PCP because PU.1 regulates the expression of a number of macrophage receptors and the differentiation of monocytes to macrophages. Studies are being carried out to prove this hypothesis.
- Lasbury ME. Durant PJ. Lee CH. Inducible nitric oxide synthase expression in Pneumocystis carinii pneumonia. Journal of Eukaryotic Microbiology. 50 Suppl:634-5, 2003.
- Lasbury ME. Lin P. Tschang D. Durant PJ. Lee CH. Effect of bronchoalveolar lavage fluid from Pneumocystis carinii-infected hosts on phagocytic activity of alveolar macrophages. Infection & Immunity. 72(4):2140-7, 2004 Apr.
- Lasbury ME. Tang X. Durant PJ. Lee CH. Effect of transcription factor GATA-2 on phagocytic activity of alveolar macrophages from Pneumocystis carinii-infected hosts. Infection & Immunity. 71(9):4943-52, 2003 Sep.
- Lee CH. Lasbury ME. Xuei X. Jerome RE. Edenberg HJ. Lu D. Durant PJ. Tschang D. Transcriptional changes in alveolar macrophages during Pneumocystis pneumonia. Journal of Eukaryotic Microbiology. 50 Suppl:645, 2003.
- Lasbury ME. Durant PJ. Lee CH. Transtracheal inoculation of Pneumocystis carinii in immunocompetent animals. Journal of Eukaryotic Microbiology. 50 Suppl:643-4, 2003.
- Lasbury ME. Lin PM. Tschang D. Durant PJ. Lee CH. Pneumocystis carinii factor responsible for reduced phagocytic activity in alveolar macrophages. Journal of Eukaryotic Microbiology. 50 Suppl:641-2, 2003.
- Lasbury ME. Durant PJ. Lee CH. Pneumocystis carinii cyst is associated with inflammation in the host. Journal of Eukaryotic Microbiology. 50 Suppl:639-40, 2003.
- Lasbury ME. Durant PJ. Lee CH. Numbers of alveolar macrophages are increased during Pneumocystis pneumonia in mice. Journal of Eukaryotic Microbiology. 50 Suppl:637-8, 2003.
- Lasbury ME. Durant PJ. Lee CH. Life cycle stage-specific and encystment protein profiles in Pneumocystis carinii. Journal of Eukaryotic Microbiology. 50 Suppl:636, 2003.
- Lasbury ME. Durant PJ. Lee CH. Environmental stress and encystment of Pneumocystis carinii. Journal of Eukaryotic Microbiology. 50 Suppl:632-3, 2003.
- Lasbury ME. Durant PJ. Lee CH. Decrease in alveolar macrophage number during Pneumocystis carinii infection. Journal of Eukaryotic Microbiology. 50 Suppl:630-1, 2003.
- Lasbury ME. Durant PJ. Bartlett MS. Smith JW. Lee CH. Correlation of organism burden and alveolar macrophage counts during infection with Pneumocystis carinii and recovery. Clinical & Diagnostic Laboratory Immunology. 10(2):293-302, 2003 Mar.