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Human microglial cells synthesize albumin in brain.

Ahn SM, Byun K, Cho K, Kim JY, Yoo JS, Kim D, Paek SH, Kim SU, Simpson RJ, Lee B - PLoS ONE (2008)

Bottom Line: In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin.Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42)- or lipopolysaccharide (LPS)-treatment.These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.

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 (Abeta), the causative agent of AD; albumin is also a potent inhibitor of Abeta 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. Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42)- or lipopolysaccharide (LPS)-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

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Related in: MedlinePlus

Albumin expression in human microglial cells.Microglial markers (CD11b or Iba-1) were co-expressed with albumin in all HMO6 cells (a) and human primary microglial cells (b). This observation was further confirmed by immunohistochemical staining of human fetal (c) and adult (d) brain tissues, in which albumin was co-expressed with CD11b or Iba-1. Anti-human-albumin antibody used for ICC and IHC does not have cross-reactivity with bovine albumin. Minimal co-localization of albumin and non-microglial markers was observed in other cell types of brain: MAP2 for neurons (e); GFAP for astrocytes (f); MBP for oligodendrocytes (g). Scale bars = 50 µm.
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pone-0002829-g001: Albumin expression in human microglial cells.Microglial markers (CD11b or Iba-1) were co-expressed with albumin in all HMO6 cells (a) and human primary microglial cells (b). This observation was further confirmed by immunohistochemical staining of human fetal (c) and adult (d) brain tissues, in which albumin was co-expressed with CD11b or Iba-1. Anti-human-albumin antibody used for ICC and IHC does not have cross-reactivity with bovine albumin. Minimal co-localization of albumin and non-microglial markers was observed in other cell types of brain: MAP2 for neurons (e); GFAP for astrocytes (f); MBP for oligodendrocytes (g). Scale bars = 50 µm.

Mentions: 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). In immunohistochemistry (IHC) study using human fetal and adult brain tissues, cells staining positive for microglial markers (CD11b and Iba1), also coexpressed albumin (Fig. 1c&d). When human adult brain tissues were double stained for albumin and non-microglial cell markers (i.e. microtubule-associated protein 2 (MAP2) for neurons; glial fibrillary acidic protein (GFAP) for astrocytes; myelin basic protein (MBP) for oligodendrocytes), minimal co-localization was observed (Fig. 1e–g).


Human microglial cells synthesize albumin in brain.

Ahn SM, Byun K, Cho K, Kim JY, Yoo JS, Kim D, Paek SH, Kim SU, Simpson RJ, Lee B - PLoS ONE (2008)

Albumin expression in human microglial cells.Microglial markers (CD11b or Iba-1) were co-expressed with albumin in all HMO6 cells (a) and human primary microglial cells (b). This observation was further confirmed by immunohistochemical staining of human fetal (c) and adult (d) brain tissues, in which albumin was co-expressed with CD11b or Iba-1. Anti-human-albumin antibody used for ICC and IHC does not have cross-reactivity with bovine albumin. Minimal co-localization of albumin and non-microglial markers was observed in other cell types of brain: MAP2 for neurons (e); GFAP for astrocytes (f); MBP for oligodendrocytes (g). Scale bars = 50 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2483733&req=5

pone-0002829-g001: Albumin expression in human microglial cells.Microglial markers (CD11b or Iba-1) were co-expressed with albumin in all HMO6 cells (a) and human primary microglial cells (b). This observation was further confirmed by immunohistochemical staining of human fetal (c) and adult (d) brain tissues, in which albumin was co-expressed with CD11b or Iba-1. Anti-human-albumin antibody used for ICC and IHC does not have cross-reactivity with bovine albumin. Minimal co-localization of albumin and non-microglial markers was observed in other cell types of brain: MAP2 for neurons (e); GFAP for astrocytes (f); MBP for oligodendrocytes (g). Scale bars = 50 µm.
Mentions: 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). In immunohistochemistry (IHC) study using human fetal and adult brain tissues, cells staining positive for microglial markers (CD11b and Iba1), also coexpressed albumin (Fig. 1c&d). When human adult brain tissues were double stained for albumin and non-microglial cell markers (i.e. microtubule-associated protein 2 (MAP2) for neurons; glial fibrillary acidic protein (GFAP) for astrocytes; myelin basic protein (MBP) for oligodendrocytes), minimal co-localization was observed (Fig. 1e–g).

Bottom Line: In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin.Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42)- or lipopolysaccharide (LPS)-treatment.These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.

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 (Abeta), the causative agent of AD; albumin is also a potent inhibitor of Abeta 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. Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42)- or lipopolysaccharide (LPS)-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

Show MeSH
Related in: MedlinePlus