Role of CD23 in astrocytes inflammatory reaction during HIV-1 related encephalitis.
Soluble factors released by intra-cerebral activated cells are implicated in neuronal alterations during central nervous system inflammatory diseases. In this study, the role of the CD23 pathway in astrocyte activation and its participation in human immunodeficiency virus-1 (HIV-1)-induced neuropathology were evaluated. In human primary astrocytes, CD23 protein membrane expression was dose-dependently upregulated by gp120. It was also upregulated by gamma-interferon (gamma-IFN) and modulated by interleukin-1-beta (IL-1beta) whereas microglial cells in these stimulation conditions did not express CD23. Cell surface stimulation of CD23 expressed by astrocytes induced production of nitric oxide (NO) and IL-1beta which was inhibited by a specific inducible NO-synthase (iNOS) inhibitor (aminoguanidine), indicating the implication of this receptor in the astrocyte inflammatory reaction. On brain tissues from five out of five patients with HIV-1-related encephalitis, CD23 was expressed by astrocytes and by some microglial cells, whereas it was not detectable on brain tissue from five of five HIV-1-infected patients without central nervous system (CNS) disease or from two of two control subjects. In addition, CD23 antigen was co-localized with iNOS and nitrotyrosine on brain tissue from patients with HIV1-related encephalitis, suggesting that CD23 participates in iNOS activation of astrocytes in vivo. In conclusion, CD23 ligation is an alternative pathway in the induction of inflammatory product synthesis by astrocytes and participates in CNS inflammation.
Dugas
N
N
Laboratoire Virus, Neurone et Immunité, Faculté de Médecine Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin Bicêtre, France.
Lacroix
C
C
Kilchherr
E
E
Delfraissy
J F
JF
Tardieu
M
M
D015526:AIDS Dementia Complex / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D009457:Neuroglia / Q000166:cytology / Q000276:immunology; D017942:Nitric Acid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D012333:RNA, Messenger; D017455:Receptors, IgE; C002744:3-nitrotyrosine; D017942:Nitric Acid; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II