Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain

Journal of Neuroinflammation
Fengjiao WuHong Zhou

Abstract

The complement system is becoming increasingly recognized as a key participant in many neurodegenerative diseases of the brain. Complement-deficient animals exhibit reduced neuroinflammation. In the present study, we administered intracerebroventricularly lipopolysaccharide (LPS) to mimic local infection of the brain and investigated the role of key complement component C3 in brain vasculature endothelial activation and leukocyte recruitment. The degree of neutrophil infiltration was determined by esterase staining. Leukocyte-endothelial interactions were measured using intravital microscopy. Cerebral endothelial activation was evaluated using real-time PCR and Western blotting. Neutrophil infiltration into the brain cortex and hippocampus was significantly reduced in C3(-/-) mice and C3aR(-/-) mice but not in C6(-/-) mice. We detected markedly attenuated leukocyte-endothelial interactions in the brain microvasculature of C3(-/-) mice. Accordingly, in response to LPS administration, the brain microvasculature in these mice had decreased expression of P-selectin, E-selectin, intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Depletion of C3 from the circulation also caused reduction ...Continue Reading

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Citations

May 29, 2016·Journal of Neuroimmunology·Charlotta E ErikssonTomas Bergström
Apr 2, 2019·Hypertension·Cheng-Chao Ruan, Ping-Jin Gao
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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

ImageJ
SPSS

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