The global hypothesis underlying this project is that interactions between natural killer (NK) cells and monocytes/macrophages (MO) are important in human defense against invading periodontopathogens. Because these cells are not restricted by the major histocompatibility complex, they are capable of a prompt response to many stimuli. By testing the interactions of lipopolysaccharides (LPS) from pathogenic and non-pathogenic oral bacteria with NK cells and MO, this project will examine NK and MO killing mechanisms and cellular regulation. It will also address the potential of cellular regulatory molecules to participate in bone destruction, a hallmark of periodontal disease. This project will focus on fundamental aspects of the pathogen-NK/MO interaction which should provide valuable information on the pathogenesis of periodontal disease. Understanding the nature of cytotoxic regulatory processes may permit the manipulation of these processes in a predictable manner for the benefit of the affected patient. To specifically address the issues of NK and MO regulation in periodontal disease, four hypotheses will be tested: 1) that NK down-regulation by LPS-stimulated MO occurs due to the production of an active intermediary, such as prostaglandins, interleukin-1 (IL-1), or tumor necrosis factor (TNF), 2) that antibodies against NK and MO adherence molecules (LFA antigens) provide a negative signal thereby blocking interferon (IFN) release by LPS and other stimulators known to induce IFN, 3) that LPS-activated NK cells and MP participate in direct killing of periodontal bacteria, and 4) that LPS from pathogenic and non-pathogenic periodontal bacteria induce dissimilar IL-1 and TNF gene expression in MO.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DE009174-05
Application #
2130461
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1989-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1995-06-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kinder Haake, S; Lindemann, R A (1997) Fusobacterium nucleatum T18 aggregates human mononuclear cells and inhibits their PHA-stimulated proliferation. J Periodontol 68:39-44
Lindemann, R A; Kinder Haake, S A; Kjeldsen, M et al. (1996) Effect of oral bacteria on peripheral blood leukocyte interleukin-6 and soluble interleukin-6 receptor production. Oral Microbiol Immunol 11:332-6
Lindemann, R A; Kjeldsen, M; Cabret, M (1995) Effect of whole oral bacteria and extracted lipopolysaccharides on peripheral blood leukocyte interleukin-2 receptor expression. J Periodontal Res 30:264-71
Lindemann, R A; Lala, A; Miyasaki, K T (1994) The in vitro effect of human polymorphonuclear leukocyte azurophil granule components on natural killer cell cytotoxicity. Oral Microbiol Immunol 9:186-92
Lala, A; Lindemann, R A; Miyasaki, K T (1992) The differential effects of polymorphonuclear leukocyte secretion on human natural killer cell activity. Oral Microbiol Immunol 7:89-95
Lindemann, R A; Franker, C K (1991) Phagocyte-mediated killing of Candida tropicalis. Mycopathologia 113:81-7
Lindemann, R A; Singh, K P; Shau, H et al. (1991) The effects of staphylococcal protein A on human lymphokine-activated killer cell induction. Cancer Immunol Immunother 33:97-102