Complement synthesis and activation in the brain of SIV-infected monkeys.
Complement is one of the most critical defence tools against cerebral infections, but uncontrolled complement biosynthesis and activation can induce profound brain tissue damage. To clarify the role of complement in the pathogenesis of AIDS-associated neurological disorders, we analysed the synthesis of complement in the brains of SIV-infected rhesus macaques. Using immunohistochemical staining we could show that the cerebral synthesis of complement factors C1q and C3 was strongly upregulated in SIV-infected monkeys compared to the spontaneous synthesis in uninfected control monkeys. Astrocytes, neurons, microglia, infiltrating macrophages and multinuclear giant cells all contribute to the high amounts of C1q and C3 in the brain. Secreted C1q and C3 are also deposited on the membrane of neurons, a prerequisite for formation of the membrane-driven lytic membrane attack complex. The membrane deposition thus might suggest complement-induced lysis of bystander neurons as a potential mechanism for cell damage during viral infection of the brain.
Speth
Cornelia
C
Institute of Hygiene and Social Medicine, Innsbruck Medical University and Ludwig-Bolthmann-Institute for AIDS Research, Fritz-Pregl-Str. 3, Innsbruck A-6020, Austria. cornelia.speth@uibk.ac.at
Williams
Kenneth
K
Hagleitner
Magdalena
M
Westmoreland
Susan
S
Rambach
Günter
G
Mohsenipour
Iradj
I
Schmitz
Jörn
J
Würzner
Reinhard
R
Lass-Flörl
Cornelia
C
Stoiber
Heribert
H
Dierich
Manfred P
MP
Maier
Hans
H
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D003167:Complement Activation / Q000502:physiology*; D015922:Complement C1q / Q000096:biosynthesis; D003176:Complement C3 / Q000096:biosynthesis; D003165:Complement System Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008253:Macaca mulatta; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015854:Up-Regulation
D003176:Complement C3; D015922:Complement C1q; D003165:Complement System Proteins