Abstract

There are three different though related objectives of the proposed studies. First, we plan to investigate the binding characteristics of platelet-activating factor to both intact cells and membrane preparation, the role of the divalent cation, calcium, and the biochemical changes that are coupled to each receptor population. Second, we wish to elucidate the mechanism(s) by which phorbol 12-myristae 13-acetate inhibits the action of the platelet-activating factor and the role of protein kinase C in this inhibition. These include measuring the effects of the phorbol esters on: binding of platelet-activating factor, phosphoinositide hydrolysis, the dissociation of the G-protein, GTPase activities, and binding of nonhydrolysable GTP analogues. Third, we plan to characterize the effects of calcium channel blockers on binding of platelet-activating factor and the biochemical changes it produces.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024935-02
Application #
3138203
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1987-09-30
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
School of Medicine & Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Yasui, K; Yamazaki, M; Miyabayashi, M et al. (1994) Signal transduction pathway in human polymorphonuclear leukocytes for chemotaxis induced by a chemotactic factor. Distinct from the pathway for superoxide anion production. J Immunol 152:5922-9
Yasui, K; Komiyama, A; Molski, T F et al. (1994) Pentoxifylline and CD14 antibody additively inhibit priming of polymorphonuclear leukocytes for enhanced release of superoxide by lipopolysaccharide: possible mechanism of these actions. Infect Immun 62:922-7
Durstin, M; McColl, S R; Gomez-Cambronero, J et al. (1993) Up-regulation of the amount of Gi alpha 2 associated with the plasma membrane in human neutrophils stimulated by granulocyte-macrophage colony-stimulating factor. Biochem J 292 ( Pt 1):183-7
Yasui, K; Becker, E L; Sha'afi, R I (1993) Lipopolysaccharide in combination with serum potentiates the stimulated activity of phospholipase D in human neutrophils via CD14. Membr Biochem 10:81-9
Gomez-Cambronero, J; Colasanto, J M; Huang, C K et al. (1993) Direct stimulation by tyrosine phosphorylation of microtubule-associated protein (MAP) kinase activity by granulocyte-macrophage colony-stimulating factor in human neutrophils. Biochem J 291 ( Pt 1):211-7
Gomez-Cambronero, J; Huang, C K; Yamazaki, M et al. (1992) Phorbol ester inhibits granulocyte-macrophage colony-stimulating factor binding and tyrosine phosphorylation. Am J Physiol 262:C276-81
Gomez-Cambronero, J; Huang, C K; Gomez-Cambronero, T M et al. (1992) Granulocyte-macrophage colony-stimulating factor-induced protein tyrosine phosphorylation of microtubule-associated protein kinase in human neutrophils. Proc Natl Acad Sci U S A 89:7551-5
Yasui, K; Becker, E L; Sha'afi, R I (1992) Lipopolysaccharide and serum cause the translocation of G-protein to the membrane and prime neutrophils via CD14. Biochem Biophys Res Commun 183:1280-6
Yamazaki, M; Molski, T F; Stevens, T et al. (1991) Modulation of leukotriene B4 and platelet-activating factor binding to neutrophils. Am J Physiol 261:C515-20
Gomez-Cambronero, J; Wang, E; Johnson, G et al. (1991) Platelet-activating factor induces tyrosine phosphorylation in human neutrophils. J Biol Chem 266:6240-5

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