The pro-apoptotic human BH3-only peptide harakiri is expressed in cryptococcus-infected perivascular macrophages in HIV-1 encephalitis patients.
In the central nervous system (CNS), HIV-1 targets mainly microglia/macrophages. Like the CD4+ T cell depletion and neuronal loss in AIDS, apoptosis is thought to be involved in eliminating infected macrophages. In this study, we examined the expression of the pro-apoptotic BH3-peptide harakiri (Hrk) in brain tissues of AIDS patients. Immunoreactivity against Hrk was positive in perivascular macrophages infiltrated into some restricted lesions. Most of these immunopositive cells contained small inclusions positive for Grocott's methenamine silver staining. Confocal laser microscopy demonstrated that Hrk expression coincided with immunoreactivities against HIV-1 and Cryptococcus neoformans. Expression of Hrk mRNA was demonstrated in these cells by in situ hybridization, which indicated that Hrk is not phagocytosed material. Some pro-apoptotic bcl-family members, including Hrk, may contribute to the delayed hypersensitive reaction in AIDS, in macrophages eliminating opportunistic infection.
Shinoe
Takashi
T
Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. tshinoe-tky@umin.ac.jp
Wanaka
Akio
A
Nikaido
Takuya
T
Kakuta
Yukio
Y
Masunaga
Atsuko
A
Shimizu
Jun
J
Duyckaerts
Charles
C
Imaizumi
Kazunori
K
Iwamoto
Aikichi
A
Kanazawa
Ichiro
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology* / Q000821:virology; D003455:Cryptococcus neoformans; D004660:Encephalitis / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016622:Silver Staining / Q000379:methods
D051017:Apoptosis Regulatory Proteins; D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; C484586:HRK protein, human; D009479:Neuropeptides; D012333:RNA, Messenger