Abstract

The experiments described in this proposal are designed to clarify the mechnisms of platelet participation in inflammation. To do this, three areas will be studied: 1) The mechanisms of platelet stimulation by inflammatory stimuli; monosodium urate crystals are potent phlogistic agents in man and occur pathologically in human gout. These crystals stimulate platelets in vitro. To elucidate the mechanism(s) whereby these agents stimulate platelets, platelet surface proteins which interact with urate crystals will be characterized. In addition, the roles of C1 and fibronectin, which have been proposed to be platelet surface receptors, in platelet stmulation by urate crystals will be evaluated. 2) The mechanism of secretion of platelet """"""""alpha granule constituents: Platelet alpha granules contain a variety of proteins which may be involved in the production of or response to tissue injury. We will elucidate the mechanism whereby the contents of these granules are released from stimulated platelets. 3) Detection of platelet activation and localization in vivo in experimentally induced inflammation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR027214-07
Application #
3155531
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1980-08-01
Project End
1990-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Zou, Wei; Izawa, Takashi; Zhu, Tingting et al. (2013) Talin1 and Rap1 are critical for osteoclast function. Mol Cell Biol 33:830-44
Cantor, Joseph M; Ginsberg, Mark H (2012) CD98 at the crossroads of adaptive immunity and cancer. J Cell Sci 125:1373-82
Kim, Chungho; Schmidt, Thomas; Cho, Eun-Gyung et al. (2012) Basic amino-acid side chains regulate transmembrane integrin signalling. Nature 481:209-13
Ye, Feng; Kim, Chungho; Ginsberg, Mark H (2012) Reconstruction of integrin activation. Blood 119:26-33
Gutierrez, Edgar; Tkachenko, Eugene; Besser, Achim et al. (2011) High refractive index silicone gels for simultaneous total internal reflection fluorescence and traction force microscopy of adherent cells. PLoS One 6:e23807
Schmid, Michael C; Avraamides, Christie J; Dippold, Holly C et al. (2011) Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3k?, a single convergent point promoting tumor inflammation and progression. Cancer Cell 19:715-27
Ring, Colleen; Ginsberg, Mark H; Haling, Jacob et al. (2011) Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. Proc Natl Acad Sci U S A 108:149-54
Tkachenko, Eugene; Sabouri-Ghomi, Mohsen; Pertz, Olivier et al. (2011) Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells. Nat Cell Biol 13:660-7
Cantor, Joseph; Slepak, Marina; Ege, Nil et al. (2011) Loss of T cell CD98 H chain specifically ablates T cell clonal expansion and protects from autoimmunity. J Immunol 187:851-60
Kummer, Christiane; Petrich, Brian G; Rose, David M et al. (2010) A small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation. J Biol Chem 285:9462-9

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