The Role of Calcium and Magnesium Ions in Uptake of β-Amyloid Peptides by Microglial Cells

Abstract

Amyloid peptides 1-40 and 1-42 (Abeta 1-40 and Abeta 1-42) are major components of diffuse and neuritic senile plaques present in the brain of patients with Alzheimers disease. Their interaction with microglial cells was studied using a system partly mimicking these plaques, which consisted in heat-killed yeast particles coated with either Abeta 1-40 or Abeta 1-42. Using these particles, it has been shown in our laboratory that LRP is involved mainly in the elimination of Abeta 1-42-coated heat-killed yeast particles and partly in that of Abeta 1-40-coated heat-killed yeast particles by microglial cells in culture. We show here that in the presence of calcium and magnesium ions extracellular chelators, namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of coated heat-killed particles was impaired. In the presence of BAPTA-AM, an intracellular chelator of calcium ions and thapsigargin, an inhibitor of the endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of Abeta 1-40-coated heat-killed yeast particles, whereas that of Abeta 1-42-coated heat-killed yeast particles was affected. These results suggest that different signaling mechanisms are involved after the internalization of Abeta 1-40 and Abeta 1-42.

CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages

“…The role of extracellular calcium in phagocytosis is, in general, thought to be relatively minor, although apparent discrepancies exist in the literature. 68,69 As 1 example, microglial cell phagocytosis of amyloid-␤ peptide was diminished in the absence of extracellular calcium (removed by EDTA). 68 In another example, the absence of calcium decreased the binding affinity of integrins to human serum albumin-coated plastic, but did not interfere with ingestion of sheep erythrocytes coated with iC3b fragments.…”

“…68,69 As 1 example, microglial cell phagocytosis of amyloid-␤ peptide was diminished in the absence of extracellular calcium (removed by EDTA). 68 In another example, the absence of calcium decreased the binding affinity of integrins to human serum albumin-coated plastic, but did not interfere with ingestion of sheep erythrocytes coated with iC3b fragments. 69 In the current study, the absence of extracellular calcium actually increased the efficiency of CD44-mediated phagocytosis.…”

Complement receptor 3 (CD11b/CD18) is implicated in the elimination of β-amyloid peptides

“…Pharmacology and to the best of our knowledge only the class A scavenger receptors (SR-A) [7] and the low-density lipoprotein receptor-related protein (LRP) [8] have been shown to directly bind Ab and mediate its engulfment by a calcium and magnesium dependent phagocytosis [9].…”

“…Because of the phagocytic capacity of microglia, their presence within the senile plaques suggests that these cells may contribute to AD pathogenesis by removing amyloid fibrils via specific receptors [6]. Studies to identify such receptors have been conducted and to the best of our knowledge only the class A scavenger receptors (SR‐A) [7] and the low‐density lipoprotein receptor‐related protein (LRP) [8] have been shown to directly bind Aβ and mediate its engulfment by a calcium and magnesium dependent phagocytosis [9].…”

Phagocytic functions of microglial cells in the central nervous system and their importance in two neurodegenerative diseases: multiple sclerosis and Alzheimer’s disease

“…In the absence of opsonins the phagocytosis of zymosan is blocked by laminarin, a soluble molecule extracted from Laminaria digitata which shares several similarities in structures with the β-D glucans [64]. The β-glucan receptors expressed by the microglial cell lines BV-2 and MAMI were shown to be fully functional in phagocytosis of unopsonized heat-killed yeast particles [65,66].…”