Abstract

This program project brings together a consortium of investigators representing biochemistry, molecular biology, cell biology, pathology, medicine, hematology, oncology, rheumatology and nephrology who, in addition to disciplinary expertise, are established researchers in the field of neutrophil biology and pathophysiology. The proposal takes the PMN membrane as its theme and presents four specific projects concerning the genomic structure of an important neutrophil adhesion protein, Phospholipid metabolism in PM membrane signal transduction, the effects of PMN membrane lipid modification on PM function, biochemistry and on inflammation in vivo, and the interface between the PMN membrane and the actin cytoskeleton. The scope of the proposed project spans the spectrum between molecular genetics, metabolism and animal pathology. Beyond the particulars of the proposal is the coming together of a critical mass of investigators and a superb advisory group dedicated to the study of nearly all aspects of the neutrophil which dictates that the whole of this project will transcend the sum of its parts.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI028465-02
Application #
3092014
Study Section
Special Emphasis Panel (SRC (60))
Project Start
1989-09-30
Project End
1994-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Shelley, C Simon; Teodoridis, Jens M; Park, Heiyoung et al. (2002) During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter. J Immunol 168:3887-93
Farokhzad, O C; Teodoridis, J M; Park, H et al. (2000) CD43 gene expression is mediated by a nuclear factor which binds pyrimidine-rich single-stranded DNA. Nucleic Acids Res 28:2256-67
Lee, J O; Rieu, P; Arnaout, M A et al. (1995) Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Cell 80:631-8
Rieu, P; Ueda, T; Haruta, I et al. (1994) The A-domain of beta 2 integrin CR3 (CD11b/CD18) is a receptor for the hookworm-derived neutrophil adhesion inhibitor NIF. J Cell Biol 127:2081-91
Bottinger, E P; Shelley, C S; Farokhzad, O C et al. (1994) The human beta 2 integrin CD18 promoter consists of two inverted Ets cis elements. Mol Cell Biol 14:2604-15
Ueda, T; Rieu, P; Brayer, J et al. (1994) Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18). Proc Natl Acad Sci U S A 91:10680-4
Robinson, D R; Xu, L L; Tateno, S et al. (1993) Suppression of autoimmune disease by dietary n-3 fatty acids. J Lipid Res 34:1435-44
Robinson, D R; Xu, L L; Knoell, C T et al. (1993) Modification of spleen phospholipid fatty acid composition by dietary fish oil and by n-3 fatty acid ethyl esters. J Lipid Res 34:1423-34
Barnett, M L; Lamb, K A; Costello, K M et al. (1993) Characterization of interleukin-8 receptors in human neutrophil membranes: regulation by guanine nucleotides. Biochim Biophys Acta 1177:275-82
Shelley, C S; Farokhzad, O C; Arnaout, M A (1993) Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene. Proc Natl Acad Sci U S A 90:5364-8

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