Abstract

The objective of this project is to continue studies that will allow the quantitation of stages of macrophage activation in tumors. This objective will be accomplished by pursual of two specific aims. First, to use an antiserum specific for p47b to conduct immunochemical studies of this marker of priming in vitro and in progressing, as well as regressing, mouse tumors. The results of these studies will increase understanding of how macrophages become primed, and will lead to determination of the frequency and distribution of this intermediate stage of activation in tumors. Second, to use nitric acid synthase (mac-NOS) to characterize tumors immunohistochemically with respect to their content of fully activated macrophages. Immunohistochemical studies will utilize semi- thin (1 micron-thick) frozen sections and a two color detection system to demonstrate primed (p47b) and fully activated (mac-NOS) macrophages in the same section of tumor. It is expected that the new knowledge gained from these studies should have broad relevance to the field of macrophage immunobiology, because it will undoubtedly be applicable to the analysis of macrophage activation for functions other than tumor cell killing, such as the killing of microbes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031199-14
Application #
2088118
Study Section
Experimental Immunology Study Section (EI)
Project Start
1987-12-01
Project End
1995-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
14
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Kansas
Department
Pathology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160

  Publications

Gao, J J; Filla, M B; Lorsbach, R B et al. (2000) Prolonged exposure of mouse macrophages to IFN-beta suppresses transcription of the inducible nitric oxide synthase gene: altered availability of transcription factor Stat1alpha. Eur J Immunol 30:1551-61
Huang, J; Roby, K F; Pace, J L et al. (1995) Cellular localization and hormonal regulation of inducible nitric oxide synthase in cycling mouse uterus. J Leukoc Biol 57:27-35
Phillips, T A; Kujubu, D A; MacKay, R J et al. (1993) The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase). J Leukoc Biol 53:411-9
Lowenstein, C J; Alley, E W; Raval, P et al. (1993) Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci U S A 90:9730-4
Lorsbach, R B; Murphy, W J; Lowenstein, C J et al. (1993) Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem 268:1908-13
Pinson, D M; Phillips, T A; Pace, J L et al. (1991) Activation-associated marker proteins: peptide mapping and their expression in macrophage cell lines. Biochem Biophys Res Commun 176:882-6
Chen, T Y; Bright, S W; Pace, J L et al. (1990) Induction of macrophage-mediated tumor cytotoxicity by a hamster monoclonal antibody with specificity for lipopolysaccharide receptor. J Immunol 145:8-12
MacKay, R J; Pace, J L; Jarpe, M A et al. (1989) Macrophage activation-associated proteins. Characterization of stimuli and conditions needed for expression of proteins 47b, 71/73, and 120. J Immunol 142:1639-45
Jarpe, M A; Hayes, M P; Russell, J K et al. (1989) Causal association of interferon-gamma with tumor regression. J Interferon Res 9:239-44
Pace, J L (1988) Synergistic interactions between IFN-gamma and IFN-beta in priming murine macrophages for tumor cell killing. J Leukoc Biol 44:514-20

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