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Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis
Abstract:
Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation.
Insights
Central nervous system (CNS) perivascular macrophages and microglia play distinct roles in multiple sclerosis (MS) pathology. Microglia digest myelin debris, while plasma cells contribute to elevated IgG levels in chronic MS.
Area of Science:
- Neuroimmunology
- Cellular pathology of the central nervous system (CNS)
Background:
- Perivascular cells in the CNS, including macrophages and microglia, are crucial in neurological diseases.
- Multiple sclerosis (MS) is characterized by demyelination and inflammation within the CNS.
- Understanding the specific roles of different immune cells in MS pathogenesis is essential.
Purpose of the Study:
- To investigate the characteristics and functions of perivascular macrophages and microglia in MS and motor neuron disease.
- To quantify immune cell populations in MS lesions and normal-appearing white matter.
- To elucidate the cellular sources of elevated immunoglobulin G (IgG) in chronic MS.
Main Methods:
- Light and electron microscopy of CNS and lymph node tissues from MS and motor neuron disease patients.
- Quantitative analysis of perivascular cell populations in MS white matter and chronic plaque tissue.
- Comparison of cellular morphology and inclusion bodies between different cell types and disease states.
Main Results:
- CNS perivascular macrophages resemble peripheral macrophages but have larger lysosomes; microglia in MS plaques contain myelin degradation products.
- Quantitative analysis revealed significantly higher plasma cell densities in chronic MS plaques compared to normal white matter.
- No plasma cells were observed in the CNS of motor neuron disease patients.
Conclusions:
- CNS perivascular macrophages are a specialized monocyte-derived population distinct from microglia.
- Both perivascular macrophages and microglia participate in myelin breakdown product digestion in MS.
- A persistent population of CNS plasma cells in chronic MS likely accounts for elevated IgG levels, suggesting ongoing antigen expression.