Abstract

Platelet-activating factor (PAF) is a phospholipid with diverse physiologic actions. One important action is the induction of polymorphonuclear leukocyte (PMN) adhesion and priming of PMNs for secretion in response to subsequent stimuli. PAF is degraded by a specific phospholipase designed PAF acetylhydrolase. We hypothesize that intracellular PAF acetylhydrolase suppresses inflammation and protects cells against oxidative damage. We will test this hypothesis by isolating a mouse genomic clone for PAF acetylhydrolase and disrupting the gene by homologous recombination in ES cells. The functional consequences of the disruption will be transgenic animals by measuring responses to a variety of inflammatory stimuli. We predict that transgenic animals will respond to stimuli with more severe and prolonged inflammatory reactions in several different tissues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK049219-05
Application #
6105686
Study Section
Project Start
1998-09-22
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Prasher, J M; Elenitoba-Johnson, K S; Kelley, L L (2001) Loss of p53 tumor suppressor function is required for in vivo progression of Friend erythroleukemia. Oncogene 20:2946-55
Mojica, M P; Perry, S S; Searles, A E et al. (2001) Phenotypic distinction and functional characterization of pro-B cells in adult mouse bone marrow. J Immunol 166:3042-51
Lok, C N; Ponka, P (2000) Identification of an erythroid active element in the transferrin receptor gene. J Biol Chem 275:24185-90
Hsieh, F F; Barnett, L A; Green, W F et al. (2000) Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27(Kip1) and inactivation of cdk2 kinase. Blood 96:2746-54
Wiesmann, A; Kim, M; Georgelas, A et al. (2000) Modulation of hematopoietic stem/progenitor cell engraftment by transforming growth factor beta. Exp Hematol 28:128-39
Spangrude, G J; Cooper, D D (2000) Paradigm shifts in stem-cell biology. Semin Hematol 37:10-Mar
Wiesmann, A; Phillips, R L; Mojica, M et al. (2000) Expression of CD27 on murine hematopoietic stem and progenitor cells. Immunity 12:193-9
Searles, A E; Pohlmann, S J; Pierce, L J et al. (2000) Rapid, B lymphoid-restricted engraftment mediated by a primitive bone marrow subpopulation. J Immunol 165:67-74
Wiesmann, A; Spangrude, G J (1999) Marrow engraftment of hematopoietic stem and progenitor cells is independent of Galphai-coupled chemokine receptors. Exp Hematol 27:946-55
Perry, S S; Kim, M; Spangrude, G J (1999) Direct effects of cyclosporin A on proliferation of hematopoietic stem and progenitor cells. Cell Transplant 8:339-44

Showing the most recent 10 out of 19 publications