Origin of macrophages in a kaolin-induced model of rat syringomyelia: a study using radiation bone marrow chimeras.

摘要

STUDY DESIGN: Animal experimental study. OBJECTIVE: To study the origin of macrophages in a rat model of syringomyelia. SUMMARY OF BACKGROUND DATA: Syringomyelia is a clinically important condition in which a cystic cavity forms within the spinal cord. This leads to significant delayed neurologic deterioration, which may be manifested as weakness, numbness, or pain. The pathophysiology and mechanism of syrinx formation remain unclear. Human autopsy findings have demonstrated a prominent accumulation of macrophages in relation to the syrinx. Similar observations have also been made in a previously established rat model of syringomyelia. Little is known about the origin and precise functions of these cells. METHODS: Syrinx formation was induced by intraparenchymal injections of kaolin within the cervical spinal cords of 30 DA rat (RT7.1) radiation bone marrow chimeras reconstituted with bone marrow from RT7.2 congeneic donors. The distribution of macrophages was evaluated at survival times of 3 days, 1 week, and 4 weeks. Immunostaining of fresh-frozen spinal cord tissue was performed using specific antibodies against rat macrophage ED1 antigen and RT7.2 allele of CD45. This allowed donor-derived hematogenous (ED1+, RT7.2+) macrophages to be distinguished from native cells (ED1+, RT7.2-). RESULTS: Central canal dilatation was seen from 1 week. This was associated with extensive accumulation of ED1+ macrophages within the spinal cord parenchyma. A large influx of bone marrow-derived (ED1+, RT7.2+) macrophages was observed. However, a considerable proportion of resident microglia (RT7.2-) also upregulated ED1. These activated microglia demonstrated distinct morphologic features. CONCLUSIONS: Large numbers of macrophages were recruited from the bone marrow in kaolin-induced rat syringomyelia. However, a significant number of resident microglia upregulated their ED1 activity and appear to provide a substantial source of macrophages.