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Ultrastructural evidence for intracellular formation of amyloid fibrils in macrophages
M Takahashi1, T Yokota, H Kawano
1First Department of Pathology, Yamaguchi University School of Medicine, Japan.
Abstract:
Early amyloid deposition in the spleen was studied by immunoelectron microscopy following the administration of rapid amyloid-inducing agents to mice. Two days after the injection of an amyloid-enhancing factor and casein solution, a small amount of amyloid material was observed at the border of the white pulp and the marginal zone (perifollicular area) and also within the white pulp. At this stage, amyloid fibrils were seen mainly in an extracellular distribution along the cytoplasmic processes of reticular cells and also in the cytoplasmic invaginations of macrophages. By immunoelectron microscopy, gold particles labelled fibrillar structures in lysosome-derived organelles in some macrophages as well as dense bodies consisted of a homogeneous, granular matrix not having any recognizable fibrillar structures. Similar immuno-labelled organelles were also observed in the amyloid resorption stage, although, at that stage, they commonly contained other phagocytized materials as well. From these findings, we suggest that at least some amyloid fibrils are polymerized in the cytoplasm of the macrophages by the proteolytic cleavage of previously pinocytized serum amyloid A protein (SAA).
Insights
This study reveals that spleen amyloid fibrils may form within macrophages by processing serum amyloid A protein (SAA). This finding offers new insights into amyloid deposition mechanisms.
Area of Science:
- Immunology
- Pathology
- Cell Biology
Background:
- Amyloid deposition in organs like the spleen is a hallmark of various diseases.
- The precise mechanisms of early amyloid fibril formation and clearance remain incompletely understood.
Purpose of the Study:
- To investigate the early stages of amyloid deposition in the spleen using immunoelectron microscopy.
- To elucidate the cellular mechanisms involved in amyloid fibril formation and resorption.
Main Methods:
- Administration of rapid amyloid-inducing agents (amyloid-enhancing factor and casein) to mice.
- Analysis of spleen tissue using immunoelectron microscopy to visualize amyloid fibrils and cellular interactions.
- Immuno-labeling techniques to identify fibrillar structures and phagocytized material within macrophages.
Main Results:
- Early amyloid material was detected in the spleen's white pulp and perifollicular areas two days post-injection.
- Amyloid fibrils were observed extracellularly along reticular cell processes and within macrophage invaginations.
- Immuno-labeled fibrillar structures and homogeneous dense bodies were identified within lysosome-derived organelles in macrophages, also seen during amyloid resorption.
Conclusions:
- Macrophages may play a crucial role in amyloid fibril polymerization.
- Amyloid fibrils could be formed intracellularly within macrophages via proteolytic cleavage of pinocytized serum amyloid A protein (SAA).
- These findings suggest a novel pathway for amyloidogenesis involving macrophage-mediated intracellular polymerization of SAA.