Premium
A role for complement components C1q and C3 in the clearance of apoptotic cells by microglia
Author(s) -
Fraser Deborah Ann,
Pisalyaput Karntipa,
Vogler Emily C.,
Tenner Andrea J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.554
Subject(s) - microglia , proinflammatory cytokine , phagocytosis , microbiology and biotechnology , inflammation , complement system , immunology , neuroinflammation , apoptosis , jurkat cells , cytokine , complement c1q , chemistry , biology , immune system , biochemistry , t cell
Microglia, the phagocytic cells of the CNS, respond to C1q with enhanced phagocytosis of suboptimally opsonsized targets, similar to other phagocytes. Since C1q is upregulated following neuronal injury and is expressed early in neurodegenerative diseases such as Alzheimer's disease, C1q may be influencing inflammation in the CNS by modulating the phagocytic functions and by directing cytokine production in microglia prior to activation of the entire complement cascade. Here we show that in vitro microglial ingestion of apoptotic neurons, neuronal blebs and early and late apoptotic Jurkat cells is enhanced by the presence of normal serum, but not with C1q or C3 depleted serum. Purified C1q bound to these apoptotic cells in a dose dependent manner, although this did not enhance their uptake by microglia, suggesting C1q alone is not sufficient for enhanced uptake. While C1q binding to apoptotic Jurkats incubated with 10% serum was not detectable, C3b binding was evident and dependent on the presence of C1q, presumably due to activation of the classical complement pathway. In a separate assay, microglia added to C1q coated wells downregulated the LPS‐induced production of proinflammatory cytokines IL‐1α, IL‐1β, IL‐6, and TNF‐α. The data are consistent with a protective role for C1q in the CNS by enhancing microglial clearance of cell debris while suppressing proinflammatory cytokines. Supported by NIH grant AI41090.