ALTERATIONS IN THE ACTIVITY OF PHOSPHOLIPASES A(2) IN POSTMORTEM WHITE-MATTER FROM PATIENTS WITH MULTIPLE-SCLEROSIS

Activities toward arachidonyl-labelled phospholipase A(2) substrates w ere assayed in fractions of white matter and cerebral cortex from cont rol subjects and in fractions of demyelinated plaque, normal-appearing white matter and cerebral cortex from subjects who died with multiple sclerosis. Membranous activity at pH 8.6 in the presence of Ca2+, cha racteristic of 14 kDa ''secretory'' phospholipase A(2), in either mult iple sclerosis white matter or cortex did not differ from controls, wh ereas membranous activity at pH 4.5 in the absence of added Ca2+, char acteristic of lysosomal enzymes was increased over controls in both pl aque and normal-appearing white matter but not cerebral cortex. Activi ty in the cytosol fraction, at pH 8.6 in the presence of Ca2+ and glyc erol characteristic of the ''cytosolic'' 85 kDa enzyme was decreased b y greater than 50% in both white matter and cortex samples from multip le sclerosis subjects. Immuno-precipitation and -blotting confirmed th at the deficient activity was largely attributable to the 85 kDa enzym e although the enzyme protein was not similarly reduced.