Abstract
Albumin, an abundant plasma protein with multifunctional properties, is mainly synthesized in the liver. Albumin has been implicated in Alzheimer's disease (AD) since it can bind to and transport amyloid beta (Aβ), the causative agent of AD; albumin is also a potent inhibitor of Aβ polymerization. Despite evidence of non-hepatic transcription of albumin in many tissues including kidney and pancreas, non-hepatic synthesis of albumin at the protein level has been rarely confirmed. In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin. Here we report, for the first time, the de novo synthesis of albumin in human microglial cells in brain. Furtherore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microgial activation by Aβ1–42- or lipopolysaccharide (LPS)-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Aβ polymerization but also increases its clearance.
Highlights
Albumin is the most abundant plasma protein with multifunctional properties such as ligand-binding and transport, maintaining the colloid osmotic pressure of plasma, and regulating neutrophil function [1]
We used immunostaining for albumin and microglial markers in human cells and brain tissues to confirm that albumin is expressed in microglial cells both in vitro and in vivo
In immunocytochemistry (ICC), all HMO6 cells were double-positive for microglial markers (CD11b [19] and Iba1 [20]) and albumin (Fig. 1a); human primary microglial cells staining positive for Iba1 coexpressed albumin (Fig. 1b)
Summary
Albumin is the most abundant plasma protein with multifunctional properties such as ligand-binding and transport, maintaining the colloid osmotic pressure of plasma, and regulating neutrophil function [1]. Despite the evidence of non-hepatic transcription of albumin in many tissues, non-hepatic synthesis of albumin at the protein level has been rarely confirmed. Yamaguchi et al [18] provided convincing evidence of albumin synthesis in bone tissues cultured in serum-, albumin-free medium.
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