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. 2008 Oct 10:7:207.
doi: 10.1186/1475-2875-7-207.

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

Peter Lackner  1 , Christian Hametner, Ronny Beer, Christoph Burger, Gregor Broessner, Raimund Helbok, Cornelia Speth, Erich Schmutzhard
Affiliations

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

Peter Lackner et al. Malar J. .

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.

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Figures

Figure 1
Figure 1
Representative Western blot experiments of complement factors C1q (A), C3 (C) and C5 (E) in brains and in sera (G-I) of animals with different clinical levels of severity of cerebral malaria (CM1-3), infected animals without CM (NCM) and non infected control animals (CNT). Alpha-tubulin (B, D, F). (+) = positive control.
Figure 2
Figure 2
Densitometric analysis of Western blots of complement factors C1q (A), C3 (B) and C5 (C) in brain homogenates of animals with different clinical levels of disease severity (CM1-3, n = 12), infected animals without CM (NCM, n = 3) and non-infected control animals (CNT, n = 4). *, p < 0.05.
Figure 3
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.
Figure 4
Figure 4
Correlation analysis of densitometric values of C1q (A) and C5 (B) and the clinical severity of the disease (SHIRPA-score) in animals with CM (n = 12). Spearman's rho and p-value are shown.
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References

    1. Schmutzhard E, Gerstenbrand F. Cerebral malaria in Tanzania. Its epidemiology, clinical symptoms and neurological long term sequelae in the light of 66 cases. Trans R Soc Trop Med Hyg. 1984;78:351–353. doi: 10.1016/0035-9203(84)90118-4. - DOI - PubMed
    1. Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther. 1998;79:1–53. doi: 10.1016/S0163-7258(98)00008-4. - DOI - PubMed
    1. Hansen DS, Siomos MA, Buckingham L, Scalzo AA, Schofield L. Regulation of Murine Cerebral Malaria Pathogenesis by CD1d-Restricted NKT Cells and the Natural Killer Complex. Immunity. 2003;18:391–402. doi: 10.1016/S1074-7613(03)00052-9. - DOI - PubMed
    1. Belnoue E, Kayibanda M, Vigario AM, Deschemin JC, Van Rooijen N, Viguier M, Snounou G, Renia L. On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria. J Immunol. 2002;169:6369–6375. - PubMed
    1. Speth C, Dierich MP, Gasque P. Neuroinvasion by pathogens: a key role of the complement system. Mol Immunol. 2002;38:669–679. doi: 10.1016/S0161-5890(01)00104-3. - DOI - PubMed

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