Date of Award

2007

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Alexandra Lucas

Abstract

: The myxomaviral serpin, Serp-1, is a highly effective anti-inflammatory agent. The mechanism by which it binds to and inhibits monocyte activation remains undefined. Serp-1 was tested for association and internalization into THP-1 monocytes and Jurkat T- cells using spectrofluorometry. FACS analysis and a range of activating agents in the presence and absence of blocking antibodies to cell surface proteins was performed. Immunoprecipitation of uPA pretreated THP-1 monocyte membrane proteins was performed, but without an untreated or silver-stained control. Ex vivo treatment of a murine peritoneal exudate was attempted, but without a negative control. Serp-1 associated with both cell types and was internalized, but isolation of the nuclear envelope was not confirmed. Association was partially inihibited in THP-1 monocytes with uPAR blocking antibodies. Spectrofluorometry revealed activation of THP-1 monocytes with uPA resulted in modest increases in Serp-1 binding compared to albumin control (p< 0.0017). Immunoprecipitation with uPAR pulled down Serp-1, filamin-B, CDllb and CD61. Association with Jurkat T-cells is CD1lb/uPAR dependent.

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