Abstract

The purpose of the proposed studies is to define molecular and cellular controls that govern the biosynthesis and secretion of complement proteins. Cell free biosynthetic studies will be conducted, structural analysis of primary translation products and elucidation of the post synthetic modifications will be accomplished with samples generated in vivo and established cell lines and primary human and experimental animal cell cultures. Cellular regulatory mechanisms will be investigated in studies of mononuclear phagocyte maturation and in isolated macrophage subpopulations. The availability of a cDNA probe for the MHC class III genes factor B and C4 will permit analysis of the transcription and post-transcriptional modifications relevant to normal gene expression and by extension to analysis of the genetic deficiencies of complement in two guinea pig strains.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020032-02
Application #
3129509
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1983-12-01
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Falus, A; Beuscher, H U; Auerbach, H S et al. (1987) Constitutive and IL 1-regulated murine complement gene expression is strain and tissue specific. J Immunol 138:856-60
Miura, N; Prentice, H L; Schneider, P M et al. (1987) Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts. J Biol Chem 262:7298-305
Perlmutter, D H; Goldberger, G; Dinarello, C A et al. (1986) Regulation of class III major histocompatibility complex gene products by interleukin-1. Science 232:850-2
Perlmutter, D H; Strunk, R C; Goldberger, G et al. (1986) Regulation of complement proteins C2 and factor B by interleukin-1 and interferon-gamma acting on transfected L cells. Mol Immunol 23:1263-6
Perlmutter, D H; Dinarello, C A; Punsal, P I et al. (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349-54
Cole, F S; Auerbach, H S; Goldberger, G et al. (1985) Tissue-specific pretranslational regulation of complement production in human mononuclear phagocytes. J Immunol 134:2610-6
Strunk, R C; Whitehead, A S; Cole, F S (1985) Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide. J Clin Invest 76:985-90
Ramadori, G; Sipe, J D; Dinarello, C A et al. (1985) Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med 162:930-42
Cole, F S; Whitehead, A S; Auerbach, H S et al. (1985) The molecular basis for genetic deficiency of the second component of human complement. N Engl J Med 313:11-6
Strunk, R C; Cole, F S; Perlmutter, D H et al. (1985) gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J Biol Chem 260:15280-5

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