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PMID: 12486098 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7.

The Journal of experimental medicine ·Vol. 196 ·No. 12 ·2002-12-16 ·Pages 1553-61

Verbovetski I, Bychkov H, Trahtemberg U, Shapira I, Hareuveni M, Ben-Tal O, Kutikov I, Gill O, Mevorach D

Abstract

Immature dendritic cells (iDCs) do not mature after uptake of apoptotic cells and may play a role in the induction of peripheral tolerance to self antigens derived from apoptotic material. The integrins, alphavbeta3, alphavbeta5, and the scavenger receptor, CD36, have been shown to mediate uptake of apoptotic cells by iDCs. However, it is not known whether the complement system, also takes part in this process. In this study we investigated the ability of iDCs to bind to apoptotic cells opsonized by iC3b. Monocyte-derived dendritic cells were offered apoptotic Jurkat cells opsonized by autologous iC3b and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate. A significant increase (P < 0.001) in the amount of cleared apoptotic cells was seen at low ratios. Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001). In addition, iDC maturation responses to CD40L and lipopolysaccharide were significantly inhibited. We conclude that opsonization of apoptotic cells by iC3b induces tolerant iDCs that are able to migrate to lymph nodes.

MeSH Terms
Antigens, CD/immunology,metabolism Apoptosis B7-2 Antigen Complement C3b/immunology Complement System Proteins/immunology,metabolism Dendritic Cells/immunology Down-Regulation Genes, MHC Class II HLA-DR Antigens/metabolism Humans Integrin alphaXbeta2/metabolism Jurkat Cells Macrophage-1 Antigen/metabolism Membrane Glycoproteins/metabolism Opsonin Proteins/immunology Receptors, CCR7 Receptors, Chemokine/metabolism Up-Regulation
Chemicals
Antigens, CD B7-2 Antigen CCR7 protein, human CD86 protein, human HLA-DR Antigens Integrin alphaXbeta2 Macrophage-1 Antigen Membrane Glycoproteins Opsonin Proteins Receptors, CCR7 Receptors, Chemokine Complement C3b Complement System Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Verbovetski Inna
The Laboratory for Cellular and Molecular Immunology, Rheumatology Unit, Department of Medicine, Hadassah Hospital and the Hebrew University. Sourasky Medical Center, Jerusalem 91120, Israel.
Bychkov Hila
Trahtemberg Uriel
Shapira Itzhak
Hareuveni Mara
Ben-Tal Ofira
Kutikov Ina
Gill Oranit
Mevorach Dror
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20020263
Published
2002-12-16
Pages
1553-61
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196062
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20020263 PMC Full Text View journal details
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