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The role of macrophages in demyelination in experimental allergic neuritis
Abstract:
The role of macrophages and serum factors in demyelination in experimental allergic neuritis (EAN) was examined by a simple in vitro method. Cultivated rabbit peritoneal macrophages, preincubated with serum obtained from rabbit EAN produced by sensitization with bovine spinal nerve roots, could agglutinate and phagocytize purified bovine or rabbit peripheral nerve myelin. Sera from normal animals or from controls given adjuvant alone could not. Adhesion and phagocytosis were inhibited if EAN sera were absorbed with peripheral nerve myelin. Rabbit red blood cells were not phagocytized by macrophages exposed to EAN serum. Concomitant to these observations, three lysosomal acid hydrolases: acid proteinase, acid phosphatase and beta-glucuronidase, were assayed with respect to their topographical and chronological distribution. In the group examined at clinical onset, increases in the specific activities were 1.5-3.0-fold in the spinal roots and 1.0-1.5-fold in the sciatic nerves compared with control. The degree of increase in total activities per whole root or sciatic nerve was much higher for specific activities. The topographical distribution of the increase closely corresponded to the histological distribution of EAN lesions. These observations suggested that the increased lysosomal activity originated from lysosomal-rich infiltrating cells. These observations strongly indicated the significant role of macrophages activated by EAN serum in the demyelination of EAN.
Insights
Macrophages activated by serum from experimental allergic neuritis (EAN) patients phagocytize myelin. This study highlights the role of these activated macrophages in EAN demyelination, suggesting therapeutic targets.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathology
Background:
- Experimental allergic neuritis (EAN) is an autoimmune disease characterized by demyelination.
- The roles of macrophages and serum factors in EAN pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the in vitro role of macrophages and serum factors in demyelination in EAN.
- To analyze the distribution and activity of lysosomal acid hydrolases during EAN.
Main Methods:
- Cultured rabbit peritoneal macrophages were incubated with serum from EAN rabbits.
- Macrophage-mediated agglutination and phagocytosis of purified myelin were assessed.
- Lysosomal acid hydrolase activities (acid proteinase, acid phosphatase, beta-glucuronidase) were measured in spinal roots and sciatic nerves.
Main Results:
- Macrophages incubated with EAN serum agglutinated and phagocytized peripheral nerve myelin.
- This phagocytosis was inhibited by absorption of EAN serum with myelin.
- Specific activities of lysosomal acid hydrolases increased significantly in spinal roots and sciatic nerves at clinical onset, correlating with lesion distribution.
Conclusions:
- EAN serum activates macrophages to phagocytize myelin, suggesting a key role in demyelination.
- Increased lysosomal enzyme activity originates from infiltrating cells, likely macrophages.
- These findings implicate activated macrophages as significant contributors to demyelination in EAN.