Anaphylatoxin Signaling in Murine Glial Cells (134.58)

Abstract

Abstract Autoimmune destruction of myelin in diseases of the CNS is known to involve several immune effector mechanisms, including complement. The brain is considered an immunoprivileged site and is protected by the blood brain barrier; however, it has been shown that complement proteins are produced locally by glial cells. It has been found that glia express receptors for anaphylatoxins, C3a and C5a. Currently, our lab is investigating the effect of anaphylatoxins on glial cell activation as well as their overall role in demyelination and remyelination pathology. To study the role of anaphylatoxins in vitro, our lab created novel adenoviral vectors to express murine C3a or C5a. To study the role of anaphylatoxin signaling in glia we treated murine astrocyte and microglial cells with C3a, C5a or both anaphylatoxins, then examined various downstream effects. Using Western blots, we found that MAPK pathway proteins, ERK1/2, were highly phosphorylated when microglia were stimulated with C5a, but not C3a. In contrast, ERK1/2 were not activated in astrocytes treated with either anaphylatoxin. Finally, C5a was able to induce chemtoaxis in J774 murine macrophages; however we did not see significant migration of primary astrocytes or BV-2 microglia. These studies suggest that anaphylatoxin signaling and/or the functional consequences of that signaling is differentially regulated in a cell-specific manner.