Aluminum excytotoxicity and neuroautotoimmunity: The role of the brain expression of CD32+ (FcγRIIa), ICAM-1+ and CD3ε in aging

Abstract

In the central nervous system (CNS) microglia are crucial for the defense of the brain against invading microorganisms, formation of tumors, and damage following trauma [1]. However, uncontrolled activation of these cells may have deleterious outcomes [2] through activation of Fcγ and the complement 3 receptors and the induction of an adaptive immune reaction [3]. Proteins contributing to this reaction are the intercellular adhesion molecule-1 (ICAM-1) [3] and CD3 molecules, among others. Both can be expressed on the glia cells before cytokine release and may facilitate an autoimmune inflammatory reaction in the brain. Round microglial cells among the pyramidal cells of the hippocampus with increased expression of CD32+ (FcγIIa) and near the site of injection of aluminum were detected immunohistochemically and indicate microglial activation at the site of aluminum injury. ICAM-1+ immunoreactivity significantly increased in the hippocampus and in the choroids plexus, indicating increased inflammation in the brain as well as increased CD3ε+ expression in the hippocampus and non-MHC-restricted T cytotoxicity after aluminum injection. The pattern of expression of CD32+ (FcγIIa receptor) near the site of aluminum injection indicates that microglia may play a phagocytic role at the site of aluminum-induced excitotoxicity in the brain. Significant expression of ICAM-1+ and CD3ε + immunoreactive cells with the clusters of ICAM-1+ in the choroid plexus suggests a consequently neurotoxic autoimmune reaction induced by microglial hyperactivation in the injured brain.