Expression of scavenger receptors in glial cells. Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid.
Astrocytes and microglia associate to amyloid plaques, a pathological hallmark of Alzheimer disease. Microglia are activated by and can phagocytose beta-amyloid (Abeta). Scavenger receptors (SRs) are among the receptors mediating the uptake of fibrillar Abeta in vitro. However, little is known about the function of the astrocytes surrounding the plaques or the nature of their interaction with Abeta. It is unknown whether glial cells bind to nonfibrillar Abeta and if binding of astrocytes to Abeta depends on the same Scavenger receptors described for microglia. We determined the binding of glia to Abeta by an adhesion assay and evaluated the presence of scavenger receptors in glial cells by immunocytochemistry, immunohistochemistry of brain sections, and immunoblot. We found that astrocytes and microglia from neonatal rats adhered in a concentration-dependent manner to surfaces coated with fibrillar Abeta or nonfibrillar Abeta. Fucoidan and poly(I), known ligands for SR-type A, inhibited adhesion of microglia and astrocytes to Abeta and also inhibited Abeta phagocytosis. In contrast, a ligand for SR-type B like low density lipoprotein, did not compete glial adhesion to Abeta. Microglia presented immunodetectable SR-BI, SR-AI/AII, RAGE, and SR-MARCO (macrophage receptor with collagenous structure, a member of the SR-A family). Astrocytes presented SR-BI and SR-MARCO. To our knowledge, this is the first description of the presence of SR-MARCO in astrocytes. Our results indicate that both microglia and astrocytes adhere to fibrillar and nonfibrillar Abeta. Adhesion was mediated by a fucoidan-sensitive receptor. We propose that SR-MARCO could be the Scavenger receptor responsible for the adhesion of astrocytes and microglia to Abeta.
Alarcón
Rodrigo
R
Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile.
Fuenzalida
Carolina
C
Santibáñez
Marcos
M
von Bernhardi
Rommy
R
D000255:Adenosine Triphosphate / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001667:Binding, Competitive; D018955:CD36 Antigens; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008024:Ligands; D017628:Microglia / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009457:Neuroglia / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010587:Phagocytosis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000378:metabolism; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013314:Stress, Mechanical
D016229:Amyloid beta-Peptides; D018955:CD36 Antigens; D008024:Ligands; C490460:MARCO protein, human; D010455:Peptides; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495125:Scarb1 protein, rat; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D007633:Keratins; D000255:Adenosine Triphosphate; D011493:Protein Kinase C