Role of CD23 in astrocytes inflammatory reaction during HIV-1 related encephalitis

Soluble factors released by intra-cerebral activated cells are implicated i n neuronal alterations during central nervous system inflammatory diseases. In this study, the role of the CD23 pathway in astrocyte activation and it s participation in human immunodeficiency virus-1 (HIV-1)-induced neuropath ology were evaluated. In human primary astrocytes, CD23 protein membrane ex pression was dose-dependently upregulated by gp120. It was also upregulated by gamma-interferon (gamma -IFN) and modulated by interleukin-1-beta (IL-1 beta) whereas microglial cells in these stimulation conditions did not exp ress CD23. Cell surface stimulation of CD23 expressed by astrocytes induced production of nitric oxide (NO) and IL-1 beta which was inhibited by a spe cific inducible NO-synthase (iNOS) inhibitor (aminoguanidine), indicating t he implication of this receptor in the astrocyte inflammatory reaction. On brain tissues from five out of five patients with HIV-1-related encephaliti s, CD23 was expressed by astrocytes and by some microglial cells, whereas i t was not detectable on brain tissue from five of five HIV-1-infected patie nts without central nervous system (CNS) disease or from two of two control subjects. In addition, CD23 antigen was co-localized with iNOS and nitroty rosine on brain tissue from patients with HIV1-related encephalitis, sugges ting that CD23 participates in iNOS activation of astrocytes in vivo. In co nclusion, CD23 ligation is an alternative pathway in the induction of infla mmatory product synthesis by astrocytes and participates in CNS inflammatio n. (C) 2001 Academic Press.