Biomedical Sciences ETDs

Publication Date

5-1-2012

Abstract

The acute phase serum protein C-reactive protein (CRP) is one of the major responding proteins during inflammation response in humans. CRP is a serum pattern recognition molecule that can bind to dead or damaged cells and bacteria to initiate their clearance through interaction with immunoglobulin receptors expressed on the surface of immune cells. Immunoglobulin receptors are traditionally thought to bind exclusively to the fragment crystallizable (Fc) region of immunoglobulins and are consequently called Fc receptors (FcRs). FcRs have been shown to play an immunoregulatory role by either exacerbating inflammatory states or potently inhibiting or reversing inflammation. CRP has been proposed to act through FcRs either promoting inflammation or resolving an inflammatory insult. Immunosuppressive properties have been demonstrated for CRP in mouse models of immune complex mediated inflammation and autoimmune disease. However, the initiating and downstream mechanisms of this process have not been investigated. This dissertation uses an adoptive cell transfer model in mice to address the immunosuppressive capacity of CRP. In this model, treatment of donor spleen cells with CRP suppresses the induced platelet clearance in recipient mice and indicates that protection by CRP is dependent on expression of FcγRI on donor macrophages and FcγRIIb in the recipient mouse. As an extension of the work characterizing CRP-FcR interactions, this dissertation also describes the IgA Fc receptor I (FcαRI) as a novel receptor for CRP. The interaction between CRP and FcαRI induces cytokine production, enhances phagocytosis and alters surface expression of FcαRI on human neutrophils. Collectively, these findings highlight key components in CRP-mediated immunosuppression and a novel receptor for CRP, indicating the complex role this ancient molecule has in the human immune system.

Keywords

C-REACTIVE PROTEIN, MACROPHAGE, CD89, Fc alpha RI, CD64

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Du Clos, Terry

First Committee Member (Chair)

Mold, Carolyn

Second Committee Member

Prossnitz, Eric

Third Committee Member

Gresham, Hattie

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