This research will be done in Poland at Faculty of Biotechnology Jagiellonian University in collaboration with Joanna Cichy as an extension of NIH grant #GM37734. The proteolytic refashioning of the cell surface and its surrounding local microenvironment is an emergent and critically important regulatory mechanism for immune cell function. The overall goal of this proposal is to define key links between proteinases, chemoattractants and adhesion molecules in regulating immune responses. Specifically, we will test the hypothesis that host-derived proteinases, through processing of an inactive chemoattractant precursor to an active chemotactic factor, contribute to recruitment of immune cells to local sites of inflammation, and that proteolytic activity on the surface of immune cells plays a key role in immune cell development. We will use molecular biology and cell biology techniques, including flow cytometry, western blot analysis, and real time RT-PCR to profile proteinases in immune cells. In addition, to dissect the functions of components of the proteolytic machinery in host-defense effector cells, we will develop fluorescently-labeled probes that will allow the enzymes to be analyzed in an activity-dependent manner by flow cytometry. The experiments proposed in this application will provide new insights into the role of proteinases in immune cell functions and offer a conceptual basis for testing the potential efficacy of proteinase inhibitors for immune-based disorders.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW007174-02
Application #
7100947
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Sina, Barbara J
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$33,208
Indirect Cost
Name
Stanford University
Department
Pathology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Kulig, Paulina; Kantyka, Tomasz; Zabel, Brian A et al. (2011) Regulation of chemerin chemoattractant and antibacterial activity by human cysteine cathepsins. J Immunol 187:1403-10
Chaimowitz, Natalia S; Martin, Rebecca K; Cichy, Joanna et al. (2011) A disintegrin and metalloproteinase 10 regulates antibody production and maintenance of lymphoid architecture. J Immunol 187:5114-22
Skrzeczy?ska-Moncznik, J; Wawro, K; Stefa?ska, A et al. (2009) Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin. Biochem Biophys Res Commun 380:323-7
Skrzeczy?ska-Moncznik, Joanna; Stefa?ska, Anna; Zabel, Brian A et al. (2009) Chemerin and the recruitment of NK cells to diseased skin. Acta Biochim Pol 56:355-60
Kulig, Paulina; Zabel, Brian A; Dubin, Grzegorz et al. (2007) Staphylococcus aureus-derived staphopain B, a potent cysteine protease activator of plasma chemerin. J Immunol 178:3713-20
Zabel, Brian A; Zuniga, Luis; Ohyama, Takao et al. (2006) Chemoattractants, extracellular proteases, and the integrated host defense response. Exp Hematol 34:1021-32