Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection

Benjamin B. Gelman, Dwayne A. Wolf, Monica Rodriguez-Wolf, A. Brian West, Abida K. Haque, Miles Cloyd

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

In patients with HIV encephalitis, activated macrophages and microglial 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 study, the presence of hydrolytic enzymes in acquired immune deficiency syndrome (AIDS)-related neurodegeneration was addressed. Activities of four lysosomal hydrolases were assayed in the frontal lobe of 69 males who died with AIDS and 31 age- matched control men. Activities of all four enzymes were increased significantly (1.6 to 3.6 times) in white o 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 and other neuropathological changes were affected as were many subjects without any clear neuropathological anomaly. Lysosomal cathepsin D immunostaining revealed increased lysosomes within perivascular macrophages, multinucleated cells, activated microglial cells and hypertrophic astrocytes. Increased enzyme activity was correlated significantly with assay results for HIV-1 DNA using the polymerase chain reaction. The release of acid hydrolases associated with cerebral HIV-1 infection could lead to unopposed hydrolysis of matrix and surface proteins. These post-translational disturbances could contribute to white matter and synaptic injury in AIDS.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalAmerican Journal of Pathology
Volume151
Issue number5
StatePublished - Nov 1 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Gelman, B. B., Wolf, D. A., Rodriguez-Wolf, M., West, A. B., Haque, A. K., & Cloyd, M. (1997). Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection. American Journal of Pathology, 151(5), 1437-1446.