SYNTHESIS AND SECRETION OF ACTIVE ALPHA(1)-ANTICHYMOTRYPSIN BY MURINEPRIMARY ASTROCYTES

Activated astrocytes have been identified as the main source of the se rine protease inhibitor alpha(1)-antichymotrypsin (ACT), an acute phas e protein that is tightly associated with amyloid plaques in Alzheimer 's disease (AD) and in normal aged human and monkey brain. We analyzed the synthesis of ACT by cultured murine astrocytes in vivo. The murin e astrocytes expressed an ACT-like antigen that crossreacted with anti bodies to human ACT. The murine ACT-like protein is secreted by the as trocytes and is able to form an SDS-resistant complex with the serine protease cathepsin G, indicating that the secreted ACT is biologically active. We conclude that cultured primary astrocytes synthesize and s ecrete murine ACT in an active form. We. therefore, suggest that the A CT present within AD plaques is locally derived from plaque-associated activated astrocytes as a part of a glia-mediated local inflammatory response that is associated with the neurodegeneration seen in AD.