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J Neurochem. 2010 Feb;112(3):733-43. doi: 10.1111/j.1471-4159.2009.06494.x. Epub 2009 Nov 16.

C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production.

Author information

1
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA. fraserd@uci.edu

Abstract

The expression of C1q, a recognition molecule of the complement system, is up-regulated following neuronal injury and is detected early in neurodegenerative disorders such as Alzheimer's disease. This multimeric protein triggers an enhancement of phagocytosis of suboptimally opsonized targets by microglia, the phagocytic cells of the CNS, similar to other phagocytes, enhances the uptake of apoptotic cells in peripheral phagocytes, and suppresses inflammatory cytokine production in human monocytes, macrophages and dendritic cells in the absence of activation of the entire complement cascade. The goal of this study was to determine if C1q could influence the inflammatory response to injury in the CNS, using primary rat microglia and neurons. The data show that microglia preferentially ingest apoptotic cells in comparison to live cells, like other professional phagocytes, that microglial ingestion of apoptotic neurons and neuronal blebs is enhanced by the presence of normal serum and that these enhanced levels of uptake are diminished in serum depleted of C1q. In addition, purified C1q bound to apoptotic neurons and neuronal blebs in a dose dependent manner, and alone triggered a significant enhancement of uptake by microglia. Microglia added to C1q coated wells or fed apoptotic neurons or neuronal blebs coated with C1q suppressed the lipopolysaccharide-induced production of proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6 and TNF-alpha, while the presence of C1q enhanced levels of the chemokine MCP-1/CCL2. The data are consistent with a protective role for C1q in the CNS during early stages of cell death by enhancing microglial clearance of apoptotic cells and suppressing proinflammatory cytokines.

PMID:
19919576
PMCID:
PMC2809134
DOI:
10.1111/j.1471-4159.2009.06494.x
[Indexed for MEDLINE]
Free PMC Article

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