PMID- 15614145
OWN - NLM
STAT- MEDLINE
DCOM- 20050131
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 78
IP  - 12
DP  - 2004 Dec 27
TI  - Vascular endothelial cells evade apoptosis triggered by human leukocyte 
      antigen-DR ligation mediated by allospecific antibodies.
PG  - 1729-39
AB  - BACKGROUND: Human leukocyte antigen (HLA)-DR ligation mediates cell death of 
      antigen-presenting cells (APC), including mature B cells, macrophages, and 
      dendritic cells. This study investigates the apoptotic effects of HLA class II 
      ligation mediated by anti-HLA antibodies on activated human vascular graft 
      endothelial cells (ECs). METHODS: HLA class II expression was examined by flow 
      cytometry using a panel of HLA-typed vascular ECs isolated from transplant donors 
      and compared with that of B lymphocytes. The apoptotic effects of anti-HLA-DR 
      monoclonal antibodies (mAbs) were investigated using viability assays, DNA 
      content analysis, and annexin-V labeling. Intracellular signaling pathways 
      mediated by HLA-DR ligation on ECs were examined by Western blotting. RESULTS: 
      Even with optimal stimulation, the expression of HLA-DR on interferon 
      (IFN)-gamma-treated ECs was quantitatively lower (3-5-fold) than that on B cells. 
      Whereas anti-HLA-DR monomorphic mAbs induced apoptosis of B cells (approximately 
      22%), no significant apoptosis of IFN-gamma-activated (DR-positive) ECs ( < 5%), 
      collected from the same donor, was observed under the same conditions. Similarly, 
      specific polymorphic anti-HLA-DR11 or -DR16 antibodies were unable to induce EC 
      apoptosis. Nevertheless, antibody-binding to HLA-DR on ECs is sufficient to 
      induce intracellular signaling, as evident in the modulation of tyrosine 
      phosphorylation and protein kinase (PK)C-alpha/beta and PKB/Akt activation. Our 
      results suggest that HLA-DR ligation induces both common and divergent signaling 
      events in ECs and B cells. CONCLUSION: Collectively, our data suggest that, in 
      contrast with professional APC, graft ECs evade apoptosis mediated by HLA-DR 
      ligation, not as a result of moderate HLA-DR expression but rather as a result of 
      a specific signaling pathway.
FAU - Le Bas-Bernardet, Stephanie
AU  - Le Bas-Bernardet S
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 643 
      Immunointervention en Allo et Xenotransplantation, Hotel-Dieu, Nantes, France.
FAU - Coupel, Stephanie
AU  - Coupel S
FAU - Chauveau, Annabelle
AU  - Chauveau A
FAU - Soulillou, Jean-Paul
AU  - Soulillou JP
FAU - Charreau, Beatrice
AU  - Charreau B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantibodies)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Apoptosis/*physiology
MH  - Arteries/cytology
MH  - B-Lymphocytes/drug effects/metabolism/physiology
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/metabolism/*physiology
MH  - HLA-DR Antigens/*immunology
MH  - Histocompatibility Antigens Class II/*immunology/metabolism
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Isoantibodies/*physiology
MH  - Signal Transduction/physiology
EDAT- 2004/12/23 09:00
MHDA- 2005/02/03 09:00
CRDT- 2004/12/23 09:00
PHST- 2004/12/23 09:00 [pubmed]
PHST- 2005/02/03 09:00 [medline]
PHST- 2004/12/23 09:00 [entrez]
AID - 00007890-200412270-00008 [pii]
AID - 10.1097/01.tp.0000147339.31581.99 [doi]
PST - ppublish
SO  - Transplantation. 2004 Dec 27;78(12):1729-39. doi: 
      10.1097/01.tp.0000147339.31581.99.