ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 2844

Intracellular Complement C3 Is Exposed on the Cell Surface upon Apoptosis Induction and Participates in the Clearance of Apoptotic Cells By Phagocytes

Lucrezia Colonna1, Christian Lood1, YuFeng Peng2, Xizhang Sun3, Lena Tanaka3, Sandip Panicker4 and Keith B. Elkon3, 1Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, 2Rheumatology, University of Washington, Seattle, WA, 3Division of Rheumatology, University of Washington, Seattle, WA, 4True North Therapeutics, South San Francisco, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: apoptotic clearance, complement, phagocytosis and systemic lupus erythematosus (SLE)

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis II: Pathogenic Targets, Genetic Variants and Apoptosis

Session Type: Abstract Submissions (ACR)

Background/Purpose The complement system has been viewed as a predominantly serum-derived host defense mechanism with multiple functions, including clearance of apoptotic cells. Defective function of the complement pathways have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Recently, intracellular complement C3 storage was demonstrated in many different cell types, and C3 activation products were shown to participate in the survival and effector cell differentiation of murine and human lymphoid cells. Despite the known role of serum-derived C3 activation products in the removal and immunosuppressive properties of dying cells, the role of intracellular C3 in clearance of apoptotic cells has never been explored. Thus, we asked whether human cells expose C3 and/or C3 activation products on their surface upon cell death induction, and whether such exposure functionally participates in their phagocytic clearance, independently of serum complement factors

Methods Apoptosis and secondary necrosis of human lymphoid cells was induced by both UV irradiation and serum starvation. C3/C3b/C3bi surface and intracellular expression on live and apoptotic human T and B primary cells as well as cell lines was monitored by flow cytometry (FACS), western blot and confocal microscopy. Macrophages were derived from circulating CD14+ monocytes by culture with M-CSF. Phagocytosis of apoptotic cells in presence or absence of serum was quantified by microscopy (phagocytic index) and by FACS with the aid of fluorescently labeled apoptotic cells

Results We observed that live human primary T and B cells, and human T and B cell lines expressed intracellular but not cell surface C3/C3bi. However, upon apoptosis induction, C3 activation products were exposed on the surface of dying cells in a time dependent manner. Detection of C3/C3bi correlated with later stages of apoptosis characterized by cell shrinkage and loss of membrane integrity (Annexin V+ PI+ cells). Confocal microscopy of unfixed cells revealed detection of C3/C3bi in a granular distribution, possibly in blebs and/or other endosomal compartments. To determine whether surface exposed C3/C3bi had functional relevance, we blocked the macrophage C3bi receptors CR3 and CR4 with antibodies, and compared phagocytosis of apoptotic cells in the absence of serum. Strikingly, functional blockade of CR3 and CR4 on human macrophages in the absence of serum specifically reduced the uptake of C3bi+ late apoptotic cells, and not that of latex beads (with an inhibition of 19.3% for CR3, 24.1% for CR4, and 48% for CR3+CR4 blockade; p= 0.182, 0.066; and 0.043, respectively)

Conclusion Our results suggest that we have uncovered a novel function of intracellular complement C3 activation products in the removal of dying cells. C3 is a very large protein of 185,000 molecular mass and penetration into tissues is likely to be limited. Cell intrinsic, serum-independent, C3-mediated clearance of apoptotic cells may therefore be of particular relevance in tissues where there is accumulation of dead cells as observed in patients with SLE, as well as under other conditions such as hypoxia reperfusion injury and stroke


Disclosure:

L. Colonna,
None;

C. Lood,
None;

Y. Peng,
None;

X. Sun,
None;

L. Tanaka,
None;

S. Panicker,
None;

K. B. Elkon,
None.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/intracellular-complement-c3-is-exposed-on-the-cell-surface-upon-apoptosis-induction-and-participates-in-the-clearance-of-apoptotic-cells-by-phagocytes/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology