Complement factors C1q, C3 and C5 in brain and serum of mice with cerebral malaria.
BACKGROUND
The patho-mechanisms leading to brain damage due to cerebral malaria (CM) are yet not fully understood. Immune-mediated and ischaemic mechanisms have been implicated. The role of complement factors C1q, C3 and C5 for the pathogenesis of CM were investigated in this study.


METHODS
C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. The clinical severity of the disease was assessed by a battery of 40 standardized tests for evaluating neurological functions in mice. Brain homogenates and sera of mice with CM, infected animals without CM and non-infected control animals were analyzed for C1q, C3 and C5 up-regulation by Western blotting.


RESULTS
Densitometric analysis of Western blots of brain homogenates yielded statistically significant differences in the levels of C1q and C5 in the analyzed groups. Correlation analysis showed a statistically significant association of C1q and C5 levels with the clinical severity of the disease. More severely affected animals showed higher levels of C1q and C5. No differences in complement levels were observed between frontal and caudal parts of the brain. Densitometric analysis of Western blot of sera yielded statistically lower levels of C1q in infected animals without CM compared to animals of the control group.


CONCLUSIONS
The current study provides direct evidence for up-regulation of complement factors C1q and C5 in the brains of animals with CM. Local complement up-regulation is a possible mechanism for brain damage in experimental cerebral malaria.
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at
Peter
P
Lackner
Christian
C
Hametner
Ronny
R
Beer
Christoph
C
Burger
Gregor
G
Broessner
Raimund
R
Helbok
Cornelia
C
Speth
Erich
E
Schmutzhard
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000276:immunology* / Q000473:pathology*; D001923:Brain Chemistry; D015922:Complement C1q / Q000032:analysis* / Q000276:immunology; D003176:Complement C3 / Q000032:analysis* / Q000276:immunology; D003182:Complement C5 / Q000032:analysis* / Q000276:immunology; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology; D012720:Severity of Illness Index; D013223:Statistics as Topic
D003176:Complement C3; D003182:Complement C5; D015922:Complement C1q