Expression of scavenger receptors in glial cells - Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid
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Date
2005
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Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Abstract
Astrocytes and microglia associate to amyloid plaques, a pathological hallmark of Alzheimer disease. Microglia are activated by and can phagocytose beta-amyloid ( A beta). Scavenger receptors ( SRs) are among the receptors mediating the uptake of fibrillar A beta in vitro. However, little is known about the function of the astrocytes surrounding the plaques or the nature of their interaction with A beta. It is unknown whether glial cells bind to nonfibrillar A beta and if binding of astrocytes to A beta depends on the same Scavenger receptors described for microglia. We determined the binding of glia to A beta 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 A beta or nonfibrillar A beta. Fucoidan and poly( I), known ligands for SR-type A, inhibited adhesion of microglia and astrocytes to A beta and also inhibited A beta phagocytosis. In contrast, a ligand for SR-type B like low density lipoprotein, did not compete glial adhesion to A beta. 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 A beta. 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 A beta.
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Keywords
LOW-DENSITY-LIPOPROTEIN, ALZHEIMERS-DISEASE BRAIN, PLAQUE CORE PROTEIN, CLASS-B, NERVOUS-SYSTEM, SENILE PLAQUES, HOST-DEFENSE, IN-VITRO, INFLAMMATORY RESPONSE, CULTURED ASTROCYTES