Innate pattern recognition receptors such as C1q, are vital for clearance of foreign and altered-self targets. C1q has a dual role in vivo: activating the inflammatory complement pathway via C1 complex formation (C1qC1r2C1s2) and direct target opsonization, which is anti-inflammatory. Here we test the hypothesis that macrophages encountering foreign targets will increase levels of all C1 subunits while macrophages encountering damaged-self targets will not. Human monocyte-derived macrophages (HMDM) were polarized or exposed to foreign or damaged-self targets. Expression of C1 subunits by M1 inflammatory macrophages generally support the hypothesis, demonstrating increased production of C1r, C1s and C1 activity. Conversely, HMDM ingestion of apoptotic cells increased expression of C1q but not C1r or C1s. Levels of complement proteins C3, and C4 were also modulated in response to different targets. These findings suggest that macrophages are fine-tuning their response according to targets they interact with, in order to modulate the local inflammatory environment. Further characterization of these changes and understanding the molecular pathways involved may provide avenues for novel therapeutic pathways.
|Advisor:||Fraser, Deborah A.|
|Commitee:||Brusslan, Judith A., Eldon, Elizabeth|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 82/4(E), Masters Abstracts International|
|Subjects:||Immunology, Cellular biology, Virology, Microbiology, Histology, Molecular biology|
|Keywords:||Innate pattern recognition receptors, C1q, Foreign targets, Altered-self targets, In vivo, C1 complex formation, Macrophages, Human monocyte-derived macrophages, Apoptotic cells, Therapeutic pathways|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be