MCP-1, MCP-2 AND MCP-3 EXPRESSION IN MULTIPLE-SCLEROSIS LESIONS - AN IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

Chemokines are low molecular weight chemotactic cytokines that have be en shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue dam age. Two major families have been defined depending on the positioning of four conserved cysteines. The CXC chemokines predominantly attract neutrophils, whereas the CC chemokines predominantly attract monocyte s and other leukocyte cell types. Members of the monocyte chemotactic protein (MCP)-1 family form a major component of the CC family of chem okines and are considered the principal chemokines involved in the rec ruitment of monocytes/macrophages and activated lymphocytes. In this s tudy we addressed the expression and distribution of MCP-1, -2 and -3 in multiple sclerosis (MS) lesions of differing ages and levels of inf lammatory activity using immunohistochemistry and in situ hybridizatio n. In acute and chronic-active MS lesions immunoreactivity for MCP-1, -2 and -3 was prominent throughout the lesion center with reactivity d iminishing abruptly at the lesion edge. Hypertrophic astrocytes were s trongly reactive and inflammatory cells showed variable reactivity. Ou tside of the lesion only hypertrophic astrocytes were reactive. The re sults obtained by in situ hybridization for MCP-1 were in agreement wi th those obtained by immunostaining. In more chronic lesions immunorea ctivity for MCP-1, -2 and -3 was considerably diminished, and in chron ic-silent lesions immunoreactivity was restricted to a few scattered r eactive astrocytes. Normal control brains showed no immunoreactivity f or MCP-1, -2 and -3. Although the cellular distribution of all three m embers of this family was similar, antibodies to MCP-3 gave prominent staining of the extracellular matrix that was not noted for MCP-1 and -2. These results support the conclusion that members of the MCP famil y of chemokines are involved in the development of MS lesions in the c entral nervous system. (C) 1998 Elsevier Science B.V. All rights reser ved.