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Apoptotic DNA binds to HLA class II molecules inhibiting antigen presentation and participating in the development of anti-inflammatory functional behavior of phagocytic macrophages.

Abstract：

: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.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Filaci G,Contini P,Fravega M,Fenoglio D,Azzarone B,Julien-Giron M,Fiocca R,Boggio M,Necchi V,De Lerma Barbaro A,Merlo A,Rizzi M,Ghio M,Setti M,Puppo F,Zanetti M,Indiveri F

doi

10.1016/s0198-8859(02)00778-4

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

9-20

issue

eissn

0198-8859

issn

1879-1166

pii

S0198885902007784

journal_volume

pub_type

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Apoptotic DNA binds to HLA class II molecules inhibiting antigen presentation and participating in the development of anti-inflammatory functional behavior of phagocytic macrophages.