Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain.
Immunohistochemical methods were used to search for Fas receptor/Fas ligand system involvement in multiple sclerosis (MS) white matter brain lesions. We found large numbers of Fas ligand (Fas-L)-bearing cells present in two acute lesions and 12 of 16 chronic MS lesions, and very few positive cells in non-inflammatory controls. Four of six brains from non-MS neuropathologic conditions associated with inflammation and white matter disease were, however, also positive for Fas-L. Double staining with cell-specific markers revealed that the pattern of ligand-positive cells in chronic MS lesions was complex and composed of several different cell types which were primarily resident glial cells with a small overlay of macrophages. Fas/APO 1 (CD95) receptor expression in MS tissue was also evaluated and marked upregulation of the receptor was found. In addition, Fas receptor was induced, but to a lesser extent, in numerous control brains. The observations that TUNEL-positive dying cells were present in MS lesions and showed excellent co-localization with Fas-L, indicate that the Fas death system may contribute to plaque pathogenesis and could lead to the development of a new category of therapeutic agents for MS.
Dowling
P
P
Neurology Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07018, USA.
Shang
G
G
Raval
S
S
Menonna
J
J
Cook
S
S
Husar
W
W
D018070:Biological Specimen Banks; D001921:Brain / Q000473:pathology*; D016923:Cell Death; D053222:Fas Ligand Protein; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000302:isolation & purification*; D009103:Multiple Sclerosis / Q000209:etiology*; D009457:Neuroglia / Q000737:chemistry / Q000473:pathology; D014018:Tissue Distribution; D015854:Up-Regulation; D019014:fas Receptor / Q000302:isolation & purification*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor