The human monocyte plays a central role in the initiation and propagation of the immune response via its role in antigen uptake, processing, and presentation for T cell specific functions. In addition to antigen-specific functions, the monocyte supports the T cell response, as well as other immunologic processes, in a generalized fashion by the secretion of soluble protein factors such as monokines, hydrolytic enzymes, and enzyme inhibitors. The research proposed herein will utilize such de novo synthesized agents as markers for studying the earliest stages of immunity activation. Experiments will focus on specific characterization of the monocyte response to chemical and biological induction agents using antibodies and nucleic acid hybridization probes along with subcellular fractionation, in order to determine the events involved in monocyte activation. Also, posttranscriptional, posttranslational secretory regulation, and surface involvement in T cell activation will be addressed. The initial studies will focus on four different markers: interleukin 1alpha (IL-1alpha); interleukin 1beta (IL-1beta); tumor necrosis factor-alpha (TNF- alpha); and a proteolytic enzyme inhibitor which may play a role in solid tumor containment (the plasminogen activator inhibitor, PAI-2). These proteins represent well characterized factors which appear to be coordinately regulated under some circumstances. The overall goal of these studies will be to elucidate the specific processes needed to support monocyte activation which is required for immunity and tumor containment.
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