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

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-alpha (TNF-alpha) mRNA expression in macrophages defined by different activation markers. The majority of TNF-alpha mRNA-positive cells were macrophages positive for the pan-macrophage marker KiM1P. A subgroup of TNF-alpha 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-alpha 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-alpha mRNA expression, while others are not. This may be important for directing therapeutic strategies against well-defined pathogenic macrophage populations.