PMID- 12507810
OWN - NLM
STAT- MEDLINE
DCOM- 20040106
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 64
IP  - 1
DP  - 2003 Jan
TI  - Apoptotic DNA binds to HLA class II molecules inhibiting antigen presentation and 
      participating in the development of anti-inflammatory functional behavior of 
      phagocytic macrophages.
PG  - 9-20
AB  - Resident macrophages are mainly responsible for the clearance of apoptotic cells 
      from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied 
      by activation of inflammatory mechanisms, unlike what happens when necrotic 
      phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on 
      macrophage cell functions. After phagocytosis of apoptotic cells macrophages were 
      unable to present an exogenous antigen to autologous antigen-specific T-cell 
      lines. The inhibition was mediated by different mechanisms including binding of 
      apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages, 
      decreased expression of co-stimulatory molecules and increased secretion of tumor 
      growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages 
      phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell 
      antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha) 
      secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic 
      bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated 
      by the binding of apoptotic DNA to macrophage HLA class II molecules as well as 
      by the activation of biological mechanisms that induce an anti-inflammatory 
      functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic 
      cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta 
      secretion. These events are likely related to the preservation of healthy tissues 
      from the onset of inflammation.
FAU - Filaci, Gilberto
AU  - Filaci G
AD  - Department of Internal Medicine and Centro di Eccellenza per le Ricerche 
      Biomediche, University of Genoa, Genoa, Italy.
FAU - Contini, Paola
AU  - Contini P
FAU - Fravega, Marco
AU  - Fravega M
FAU - Fenoglio, Daniela
AU  - Fenoglio D
FAU - Azzarone, Bruno
AU  - Azzarone B
FAU - Julien-Giron, Michel
AU  - Julien-Giron M
FAU - Fiocca, Roberto
AU  - Fiocca R
FAU - Boggio, Maurizio
AU  - Boggio M
FAU - Necchi, Vittorio
AU  - Necchi V
FAU - De Lerma Barbaro, Andrea
AU  - De Lerma Barbaro A
FAU - Merlo, Andrea
AU  - Merlo A
FAU - Rizzi, Marta
AU  - Rizzi M
FAU - Ghio, Massimo
AU  - Ghio M
FAU - Setti, Maurizio
AU  - Setti M
FAU - Puppo, Francesco
AU  - Puppo F
FAU - Zanetti, Maurizio
AU  - Zanetti M
FAU - Indiveri, Francesco
AU  - Indiveri F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Apoptosis/*immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Jurkat Cells
MH  - Macrophages/cytology/*immunology/metabolism
MH  - Phagocytes/immunology
MH  - Phagocytosis/*immunology
EDAT- 2003/01/01 04:00
MHDA- 2004/01/07 05:00
CRDT- 2003/01/01 04:00
PHST- 2003/01/01 04:00 [pubmed]
PHST- 2004/01/07 05:00 [medline]
PHST- 2003/01/01 04:00 [entrez]
AID - S0198885902007784 [pii]
AID - 10.1016/s0198-8859(02)00778-4 [doi]
PST - ppublish
SO  - Hum Immunol. 2003 Jan;64(1):9-20. doi: 10.1016/s0198-8859(02)00778-4.