MONONUCLEAR PHAGOCYTE HYDROLYTIC ENZYME-ACTIVITY ASSOCIATED WITH CEREBRAL HIV-1 INFECTION

In patients with HIV encephalitis, activated macrophages and microglia l cells in the brain are infected by the human immunodeficiency virus (HIV-1), Immune activation can release neurotoxic chemicals including cytokines, free radicals, autocoids, and hydrolytic enzymes, In this s tudy, the presence of hydrolytic enzymes in acquired immune deficiency syndrome (AIDS)-related neurodegeneration was addressed. Activities o f four lysosomal hydrolases were assayed in the frontal lobe of 69 mal es who died with AIDS and 31 age-matched control men, Activities of al l four enzymes were increased significantly (1.6 to 3.6 times) in whit e matter of patients with AIDS, Less pronounced increases were present in cerebral cortex, Of 69 of the subjects with AIDS, 50 (72%), had at least one abnormally active enzyme. Patients with HIV encephalitis an d other neuropathological changes were affected as were many subjects without any clear neuropathological anomaly, Lysosomal cathepsin D imm unostaining revealed increased lysosomes within perivascular macrophag es, multinucleated cells, activated microglial cells, and hypertrophic astrocytes, Increased enzyme activity was correlated significantly wi th assay results for HIV-1 DNA using the polymerase chain reaction, Th e release of acid hydrolases associated with cerebral HIV-1 infection could lead to unopposed hydrolysis of matrix and surface proteins. The se post-translational disturbances could contribute to white matter an d synaptic injury in AIDS.