Abstract

This search project comprises the continued elucidation of the inflammatory, immunoregulatory and reparative aspects of the parasite egg-induced granulomas in murine schistosomiasis mansoni. Our long term objective is to elucidate the dynamics of cell-cell interation, idnetify and define the function of molecular mediators and enzymes which participate in the evolution and involution of thegranulomatous response. A better understanding of the regulation of inflammation, tissue damage and healing in the murine model will greatly improve the clinical handling of schistosomiasis. The research objectives are divided into 4 interrelated areas: I. Analysis of T cell circuitry active in the immunomodulation of the granuloma. This will be carried out with isolated subpopulations of splenic and granuloma T lymphocytes, Adoptive cell transfers, in vitro cell-cell interactions, the production and functional examination of soluble regulatory/amplifier molecules will be employed. II. Studies on the accessory/regulatory role of granuloma macrophages. Macrophages will be isolated from vigorous and modulated granulomas and their accessory role in the elicitation of SEA-specific secondary immune response will be examined. Production of activating and inhibitory substances by these macrophages will be tested. III. Studies on the presence and role of angiotensins I, II and prostaglandins in the granulomatous response. Vigorous and modulated granulomas will be assayed for the presence of angiotensins and prostaglandins which may play important roles in the inflammatory/regulatory aspects of the granulomatous response. The effect of immunomanipulationon the levels of these substances within the granulomas will be assayed. IV. Studies on the effect of immunomaipulation on liver collagen content and breakdown. Liver and granuloma collagen content as well as the presence of degradative neutral proteases in the virorous or modulated granulomas will be examined. The source of neutral proteases within the lesions will be localized. The class of degradative enzymes and their potential inhibitors will be identified. The effect of immunomanipulation on total collagen content, and activity of collagenease, elastase enzymes will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI012913-10
Application #
3444456
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1979-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Singh, K P; Gerard, H C; Hudson, A P et al. (2006) Differential expression of collagen, MMP, TIMP and fibrogenic-cytokine genes in the granulomatous colon of Schistosoma mansoni-infected mice. Ann Trop Med Parasitol 100:611-20
Boros, D L; Singh, K P; Gerard, H C et al. (2005) A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis. J Cell Physiol 204:370-4
Singh, Kameshwar P; Gerard, Herve C; Hudson, Alan P et al. (2005) Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in Schistosoma mansoni infected mice. Immunology 114:410-7
Singh, K P; Gerard, H C; Hudson, A P et al. (2004) Dynamics of collagen, MMP and TIMP gene expression during the granulomatous, fibrotic process induced by Schistosoma mansoni eggs. Ann Trop Med Parasitol 98:581-93
Singh, Kameshwar P; Gerard, Herve C; Hudson, Alan P et al. (2004) Expression of matrix metalloproteinases and their inhibitors during the resorption of schistosome egg-induced fibrosis in praziquantel-treated mice. Immunology 111:343-52
Cutroneo, Kenneth R; Boros, Dov L (2002) Rational basis for oligodeoxynucleotides to inhibit collagen synthesis in lung fibroblasts and primary fibroblasts from liver granulomas of Schistosoma mansoni-infected mice. Cancer Lett 180:145-51
Loeffler, David A; Lundy, Steven K; Singh, Kameshwar P et al. (2002) Soluble egg antigens from Schistosoma mansoni induce angiogenesis-related processes by up-regulating vascular endothelial growth factor in human endothelial cells. J Infect Dis 185:1650-6
Lundy, Steven K; Boros, Dov L (2002) Fas ligand-expressing B-1a lymphocytes mediate CD4(+)-T-cell apoptosis during schistosomal infection: induction by interleukin 4 (IL-4) and IL-10. Infect Immun 70:812-9
Lundy, S K; Lerman, S P; Boros, D L (2001) Soluble egg antigen-stimulated T helper lymphocyte apoptosis and evidence for cell death mediated by FasL(+) T and B cells during murine Schistosoma mansoni infection. Infect Immun 69:271-80
Chen, Y; Boros, D L (2001) The Schistosoma mansoni egg-derived r38 peptide-induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth. Parasite Immunol 23:43-50

Showing the most recent 10 out of 46 publications