Abstract
One of the crucial key targets in treatment of diseases are cell surface proteins, such as receptor complexes, and their associated signaling pathways. The Fc receptor is one of the most important phagocytic receptors of the cells of immune system. The ligand of the Fc gamma receptor is immunoglobulin G (IgG), which triggers the engulfment of foreign molecules coated by antibodies by a process called phagocytosis. A Specialized subset of cells including macrophages engulfs foreign particles by the Fc receptor. Another phagocytic receptor of macrophages is the CD36 receptor, which binds the ligand oxLDL and is known to be involved in the development of atherosclerotic lesions in the arteries. A few members of the Tetraspanin proteins have been found to be associated with theses receptors in macrophages. Tetraspanins may act as “molecular facilitators” grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. There is a significant amount of research done on the receptors of the surface of macrophages, however, the proteins associated with these receptors, their potential signaling pathways and the mechanisms involved are not yet fully understood. This thesis aims to investigate the presence and potential functional role of the specific Tetraspanin isoforms in Fc and CD36 mediated phagocytosis. Silencing RNA, quantitative assays of phagocytosis, and laser scanning confocal microscopy were used to test the phagocytic efficiency of macrophages in IgG and oxLDL mediated phagocytosis. Understanding the regulatory roles of Tetraspanins can provide insight into various immune diseases.
Highlights
The immune system defends the body against infectious organisms and foreign invaders that can cause various diseases
Manual inspection of Tetraspanin proteins identified by Ligand affinity receptor chromatography (LARC) along with the controls was performed in order to select the potential candidates that are involved with the uptake of oxLDL and Immunoglobulin g (IgG) from this family
In the table below the Larc-oxldl column shows the number of times that the following Tetraspanins were identified when oxLDL coated beads were incubated with U937 cells
Summary
Background The immune system defends the body against infectious organisms and foreign invaders that can cause various diseases. The adaptive immune system produces antibodies in response to antigens belonging to a pathogen that has previously infected the body. The innate immune system is the first line of defense in the body and it consists of cells and proteins that fight microbes or invaders at the site of infection. Cells such as macrophages are able to recognize pathogens, internalize and destroy them. The Fc receptor connects the adaptive and innate responses (Florentinus et al, 2011) Another phagocytic receptor of the macrophages is CD36, which is a class B scavenger receptor and is known for its capacity to internalize modified low-density lipoproteins (LDL).
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