Mycobacterial infection and disease both with Mycobacterium avium/Mycobacterium intracellular complex and Mycobacterium tuberculosis have emerged as a leading cause of disease in Acquired Immunodeficiency Syndrome (AIDS). The mononuclear phagocyte system is the host defense system that is most important in the body's handling of mycobacteria. Little is known about the handling of mycobacterial in the human mononuclear phagocyte system in the normal host, and probably nothing in AIDS patients. This study proposes to systemically evaluate the ability of peripheral blood monocytes and alveolar macrophages from normal human hosts and from victims of AIDS to ingest and kill Mycobacterium avium/Mycobacterium intracellular complex organisms in vitro. Peripheral blood monocytes will be obtained via venipuncture and alveolar macrophages via lung lavage during fiberoptic bronchoscopy. AIDS subjects will come from patients currently undergoing treatment at Georgetown University Hospital. Age and sex-matched normal healthy volunteers to be used as controls will come from the student body at Georgetown University. Also, the study proposes to evaluate the role(s) of immunomodulators such as complement, interleukins, prostaglandins, and interferons in enhancing or depressing both ingestion and cidal activity in the phagocytes. It is anticipated that the results from this study will lead to a better understanding of the pathogenesis of mycobacterial disease in AIDS victims, and in time lead to improved methods of treatment and/or prevention of mycobacterial disease in AIDS victims.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025849-02
Application #
3139534
Study Section
(SRC)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Katz, P; Yeager Jr, H; Whalen, G et al. (1990) Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes. J Clin Immunol 10:71-7
Swartz, R P; Naai, D; Vogel, C W et al. (1988) Differences in uptake of mycobacteria by human monocytes: a role for complement. Infect Immun 56:2223-7