ENHANCED EXPRESSION OF CHEMOTACTIC RECEPTORS IN MULTIPLE-SCLEROSIS LESIONS

We have previously shown that astrocytes and microglia express the rec eptors for C5a, interleukin-8 (IL-8) and N-formyl-Met-Leu-Phe (FMLP) i n vitro. The expression and function of chemotactic receptors in the c entral nervous system (CNS) is, however, largely unexplored. In this s tudy, we examined tissue sections from normal human brain and active, chronic active and chronic silent multiple sclerosis (MS) lesions for the expression of the receptors for C5a, IL-8 and FMLP by immunohistoc hemistry. In normal brain tissue, the expression of all three receptor s was seen at low levels on astrocytes and microglia. In contrast, exp ression for all three receptors was markedly elevated on foamy macroph ages in the acute and chronic active MS lesions. In addition, fibrous astrocytes stained intensely for the C5a receptor in the chronic activ e disease. Receptor expression in the chronic silent lesion was low an d similar to that seen in normal brain, with staining confined to a fe w hypertrophic astrocytes and foamy macrophages. These are the first s tudies to demonstrate expression of these receptors in the CNS and ele vated receptor expression in inflammatory MS lesions. The data suggest that these chemotactic receptors may play a role in inflammatory resp onses in MS and possibly in other CNS diseases.