Monocyte/macrophage differentiation was studied in biopsy samples of m
ultiple sclerosis (MS) lesions obtained in the early course of the dis
ease. Macrophages were identified by immunocytochemistry using a panel
of antibodies recognizing different macrophage-activation antigens. T
he number of cells stained with each antibody was related to the demye
linating activity of the lesions as detected by the presence of myelin
degradation products. The pan-macrophage marker Ki-M1P revealed the h
ighest numbers of macrophages in early and late active lesions. Lower
numbers were encountered in inactive, demyelinated, or remyelinated le
sions. The acute stage inflammatory macrophage markers MRP14 and 27E10
were expressed in either only early active (MRP14) or early and late
active (27E10) lesions, thus allowing the identification of actively d
emyelinating lesions. The chronic stage inflammatory macrophage marker
25F9, in contrast, showed increasing expression with decreasing lesio
nal activity. These findings indicate a differentiated pattern of macr
ophage activation in MS lesions and allow the staging of demyelinating
lesions in routinely fixed and paraffin-embedded tissue.