Identification of macrophage populations expressing tumor necrosis factor-α mRNA in acute multiple sclerosis

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Abstract
Macrophages are involved in central nervous system (CNS) demyelination in multiple sclerosis (MS) and other demyelinating diseases. Macrophages seen in MS lesions form a heterogeneous population with respect to their stage of activation and differentiation. We have analyzed macrophages from active demyelinating lesions of a patient who died from fulminant MS of Marburg’s type to define the functional heterogeneity of different macrophage populations in acute demyelination. We examined tumor necrosis factor-α (TNF-α) mRNA expression in macrophages defined by different activation markers. The majority of TNF-α mRNA-positive cells were macrophages positive for the pan-macrophage marker KiM1P. A subgroup of TNF-α mRNA-positive macrophages was stained by the early activation marker MRP14. In contrast, macrophages positive for the acute activation marker 27E10 were entirely negative for TNF-α mRNA. In conclusion, macrophages in acute demyelinating CNS lesions are heterogeneous as shown by staining for different activation markers. This heterogeneity is also of functional relevance as certain subpopulations are involved in TNF-α mRNA expression, while others are not. This may be important for directing therapeutic strategies against well-defined pathogenic macrophage populations.

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