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The Journal of Neuroscience, May 1, 1999, 19(9):3440-3447

FcRII/CD23 Is Expressed in Parkinson's Disease and Induces, In Vitro, Production of Nitric Oxide and Tumor Necrosis Factor- in Glial Cells

Stéphane Hunot¹, Nathalie Dugas², Baptiste Faucheux¹, Andreas Hartmann¹, Marc Tardieu², Patrice Debré³, Yves Agid¹, Bernard Dugas^{3, 4}, and Etienne C. Hirsch¹

¹ Institut National de la Santé et de la Recherche Médicale, Unité 289, Mécanismes et Conséquences de la Mort Neuronale, Hôpital de la Salpêtrière, F-75013 Paris, France, ² Laboratoire "Virus, Neurone et Immunité," Unité de Formation et de Recherche Kremlin Bicêtre, F-94276 Le Kremlin-Bicêtre Cedex, France, ³ Centre National de la Recherche Scientifique, Unité de Recherche Associée 625, Laboratoire d'Immunologie Cellulaire et Tissulaire, Hôpital de la Salpêtrière, F-75013 Paris, France, and ⁴ Oxykine Therapeutics, F-75116 Paris, France

Oxidative stress is thought to be involved in the mechanism of nerve cell death in Parkinson's disease (PD). Among several toxic oxidative species, nitric oxide (NO) has been proposed as a key element on the basis of the increased density of glial cells expressing inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of patients with PD. However, the mechanism of iNOS induction in the CNS is poorly understood, especially under pathological conditions. Because cytokines and FcRII/CD23 antigen have been implicated in the induction of iNOS in the immune system, we investigated their role in glial cells in vitro and in the SN of patients with PD and matched control subjects. We show that, in vitro, interferon- (IFN-) together with interleukin-1 (Il-1) and tumor necrosis factor- (TNF-) can induce the expression of CD23 in glial cells. Ligation of CD23 with specific antibodies resulted in the induction of iNOS and the subsequent release of NO. The activation of CD23 also led to an upregulation of TNF- production, which was dependent on NO release. In the SN of PD patients, a significant increase in the density of glial cells expressing TNF-, Il-1, and IFN- was observed. Furthermore, although CD23 was not detectable in the SN of control subjects, it was found in both astroglial and microglial cells in parkinsonian patients. Altogether, these data demonstrate the existence of a cytokine/CD23-dependent activation pathway of iNOS and of proinflammatory mediators in glial cells and their involvement in the pathophysiology of PD.

Key words: inflammation; iNOS; astrocytes; microglial cells; neurodegenerative disease; postmortem

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1993440-08$05.00/0

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