PMID- 16099886
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 12
DP  - 2005 Dec 1
TI  - Oxidized beta2-glycoprotein I induces human dendritic cell maturation and 
      promotes a T helper type 1 response.
PG  - 3880-7
AB  - The human plasma protein beta2-glycoprotein I (beta2-GPI) is the most common 
      target for antiphospholipid antibodies associated with thrombotic events in 
      chronic disorders related to endothelial cell dysfunction. Crucial information is 
      needed to clarify why this self-abundant protein is targeted by autoimmune 
      responses. In this study, we investigated whether oxidative modification of 
      beta2-GPI, either spontaneous in culture wells or induced by treatment with H2O2, 
      renders this self-protein able to activate immature monocyte-derived dendritic 
      cells (DCs) from healthy human donors. Oxidized beta2-GPI caused DCs to mature so 
      that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related 
      (HLA-DR), and CD40 increased. The interaction between oxidized beta2-GPI and DCs 
      specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1beta, 
      IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-10. Oxidized 
      beta2-GPI-stimulated DCs had increased allostimulatory ability and primed naive T 
      lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between 
      oxidized beta2-GPI and DCs involved interleukin-1 receptor associated kinase 
      (IRAK) phosphorylation and nuclear factor kappaB (NFkappaB) activation. 
      Pretreatment of beta2-GPI with the antioxidant alpha-tocopherol prevented DC 
      maturation. These findings show that human oxidized beta2-GPI, probably by 
      interacting with a member of the Toll-like receptor (TLR) family, causes DCs to 
      mature. Because this key beta2-GPI function requires oxidative modification, in 
      several chronic disorders related to endothelial cell dysfunction oxidative 
      stress might trigger the "autoimmune spiral."
FAU - Buttari, Brigitta
AU  - Buttari B
AD  - Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto 
      Superiore di Sanita, Rome, Italy.
FAU - Profumo, Elisabetta
AU  - Profumo E
FAU - Mattei, Vincenzo
AU  - Mattei V
FAU - Siracusano, Alessandra
AU  - Siracusano A
FAU - Ortona, Elena
AU  - Ortona E
FAU - Margutti, Paola
AU  - Margutti P
FAU - Salvati, Bruno
AU  - Salvati B
FAU - Sorice, Maurizio
AU  - Sorice M
FAU - Rigano, Rachele
AU  - Rigano R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050811
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Glycoproteins)
RN  - 0 (Interleukins)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Cell Communication/immunology
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Glycoproteins/*immunology/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Interleukins/immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*immunology
MH  - Th1 Cells/*immunology
MH  - beta 2-Glycoprotein I
EDAT- 2005/08/16 09:00
MHDA- 2006/01/19 09:00
CRDT- 2005/08/16 09:00
PHST- 2005/08/16 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/08/16 09:00 [entrez]
AID - S0006-4971(20)66925-7 [pii]
AID - 10.1182/blood-2005-03-1201 [doi]
PST - ppublish
SO  - Blood. 2005 Dec 1;106(12):3880-7. doi: 10.1182/blood-2005-03-1201. Epub 2005 Aug 
      11.