iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-κB-dependent blockade

Gil Amarilyo, Inna Verbovetski, Mizhir Atallah, Amir Grau, Giora Wiser, Oranit Gil, Ynon Ben-Neriah, Dror Mevorach

Research output: Contribution to journalArticlepeer-review

Abstract

In recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune-inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complementdependent system of apoptotic cell clearance by human-derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non-opsonic zymosan, we show that iC3b-apoptotic cells induce NF-jB inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post-transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b-opsonized apoptotic cells is characterized by macrophage secretion of IL-10 and lack of TGF-β secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct antiinflammatory response and transcriptional NF-κB-dependent blockage.

Original languageEnglish
Pages (from-to)699-709
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Complement
  • iC3b
  • NF-κB

Fingerprint

Dive into the research topics of 'iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-κB-dependent blockade'. Together they form a unique fingerprint.

Cite this