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 #
5R01AI024836-05
Application #
3138047
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1986-06-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Schmidt, B Z; Fowler, N L; Hidvegi, T et al. (1999) Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. J Biol Chem 274:11782-8
Wang, X; Circolo, A; Lokki, M L et al. (1998) Molecular heterogeneity in deficiency of complement protein C2 type I. Immunology 93:184-91
Matsumoto, M; Fukuda, W; Circolo, A et al. (1997) Abrogation of the alternative complement pathway by targeted deletion of murine factor B. Proc Natl Acad Sci U S A 94:8720-5
Ernst, S C; Circolo, A; Davis 3rd, A E et al. (1996) Impaired production of both normal and mutant C1 inhibitor proteins in type I hereditary angioedema with a duplication in exon 8. J Immunol 157:405-10
Garnier, G; Circolo, A; Colten, H R (1996) Constitutive expression of murine complement factor B gene is regulated by the interaction of its upstream promoter with hepatocyte nuclear factor 4. J Biol Chem 271:30205-11
Katz, Y; Gur, S; Aladjem, M et al. (1995) Synthesis of complement proteins in amnion. J Clin Endocrinol Metab 80:2027-32
Wang, X; Fleischer, D T; Whitehead, W T et al. (1995) Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African-American families. J Immunol 154:5464-71
Akama, H; Johnson, C A; Colten, H R (1995) Human complement protein C2. Alternative splicing generates templates for secreted and intracellular C2 proteins. J Biol Chem 270:2674-8
Kulics, J; Circolo, A; Strunk, R C et al. (1994) Regulation of synthesis of complement protein C4 in human fibroblasts: cell- and gene-specific effects of cytokines and lipopolysaccharide. Immunology 82:509-15
Strunk, R C; Fleischer, J A; Katz, Y et al. (1994) Developmentally regulated effects of lipopolysaccharide on biosynthesis of the third component of complement and factor B in human fibroblasts and monocytes. Immunology 82:314-20

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