This application presents an experimental approach based on the extensive knowledge in the literature on c-reactive protein (CRP). This study integrates the reports on CRP to present a cohesive concept, which can appropriately be carried out to understand the role of CRP in inflammation, tissue injury, diseases and its role in cancer immunomodulation.
The specific aims of this proposal are to achieve an understanding of CRP functions based on the following premises: 1) the primary function of CRP is that of a non-specific binder of tissue residues from injury. These residues include polysaccharides, nucleic acids, lipids, glycoproteins and polypeptides. This binding appears to require calcium ions. (2) These complexes with CRP leads to the secondary functions such as the activation of completment and especially through the activation of monocytes to induce production of monokines. The primary emphasis in this study is to examine this hypothesized primary and secondary functions of CRP. The first phase will be studied by examination of labeled residues with CRP and the complexes precipitated with anti-CRP. The secondary aspects of CRP functions will examined the effects of these complexes on monocyte activation. For example, PAF-CRP complexes activates monocytes via the Fc Receptors to induce high levels of interleukin 1 production. It is hoped to examine whether monocytes stimulated by CRP- complexes also induce tumor necrosis factor (TNF) and through T4 cells induced by IL-1 from monocytes produce elevated levels of interleukin 2. Thus, this study will include assessment of IL-l by immunofluorescence and mouse thymocyte assay and TNF by its killing of mouse tumor target cells in culture.
