Limits...
Complement factors C1q, C3 and C5 in brain and serum of mice with cerebral malaria.

Lackner P, Hametner C, Beer R, Burger C, Broessner G, Helbok R, Speth C, Schmutzhard E - Malar. J. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

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.

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Densitometric analysis of Western blots of complement factors C1q (A), C3 (B) and C5 (C) in sera of animals with different clinical levels of severity of cerebral malaria (CM1-3, n = 12), infected animals without CM (NCM, n = 3) and non-infected control animals (CNT, n = 4). **, p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2572067&req=5

Figure 3: Densitometric analysis of Western blots of complement factors C1q (A), C3 (B) and C5 (C) in sera of animals with different clinical levels of severity of cerebral malaria (CM1-3, n = 12), infected animals without CM (NCM, n = 3) and non-infected control animals (CNT, n = 4). **, p < 0.01.

Mentions: C1q levels in brain homogenates showed a statistically significant difference in the analyzed groups (Figures 1A and 2A; Kruskal-Wallis test; p < 0.05). Post-hoc analysis did not show significant differences between the respective groups of interest. In mice with CM, Spearmen's Rho indicated a significant correlation of C1q complement values in brain homogenates and the clinical severity score (Figure 4A; rho = -0.64, p < 0.05), i.e. animals with more severe disease showed higher levels of brain C1q. Densitometric measures of C1q in sera of the studied animals revealed a statistically significant difference (Figure 3A). Post hoc analysis yielded significantly lower values in NCM animals compared to non infected control animals (Figures 1G and 3A).


Complement factors C1q, C3 and C5 in brain and serum of mice with cerebral malaria.

Lackner P, Hametner C, Beer R, Burger C, Broessner G, Helbok R, Speth C, Schmutzhard E - Malar. J. (2008)

Densitometric analysis of Western blots of complement factors C1q (A), C3 (B) and C5 (C) in sera of animals with different clinical levels of severity of cerebral malaria (CM1-3, n = 12), infected animals without CM (NCM, n = 3) and non-infected control animals (CNT, n = 4). **, p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572067&req=5

Figure 3: Densitometric analysis of Western blots of complement factors C1q (A), C3 (B) and C5 (C) in sera of animals with different clinical levels of severity of cerebral malaria (CM1-3, n = 12), infected animals without CM (NCM, n = 3) and non-infected control animals (CNT, n = 4). **, p < 0.01.
Mentions: C1q levels in brain homogenates showed a statistically significant difference in the analyzed groups (Figures 1A and 2A; Kruskal-Wallis test; p < 0.05). Post-hoc analysis did not show significant differences between the respective groups of interest. In mice with CM, Spearmen's Rho indicated a significant correlation of C1q complement values in brain homogenates and the clinical severity score (Figure 4A; rho = -0.64, p < 0.05), i.e. animals with more severe disease showed higher levels of brain C1q. Densitometric measures of C1q in sera of the studied animals revealed a statistically significant difference (Figure 3A). Post hoc analysis yielded significantly lower values in NCM animals compared to non infected control animals (Figures 1G and 3A).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus