Proteinase Regulators of Immune Cell Traffic Mechanisms

Stanford University, Stanford CA

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Abstract

DESCRIPTION (provided by applicant): 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.