iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-kappaB-dependent blockade.
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 complement-dependent 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-kappaB 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-beta secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-kappaB-dependent blockage.
Amarilyo
Gil
G
The Laboratory for Cellular and Molecular Immunology and Rheumatology Research Center, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. gamarilyo@mednet.ucla.edu
Verbovetski
Inna
I
Atallah
Mizhir
M
Grau
Amir
A
Wiser
Giora
G
Gil
Oranit
O
Ben-Neriah
Ynon
Y
Mevorach
Dror
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002469:Cell Separation; D003179:Complement C3b / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D003179:Complement C3b