PMID- 15993779
OWN - NLM
STAT- MEDLINE
DCOM- 20051101
LR  - 20071114
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 24
IP  - 7 Suppl
DP  - 2005 Jul
TI  - Inhibition of obliterative airway disease development following heterotopic 
      murine tracheal transplantation by costimulatory molecule blockade using 
      anti-CD40 ligand alone or in combination with donor bone marrow.
PG  - S232-8
AB  - INTRODUCTION: Obliterative airway disease (OAD) development in heterotopic murine 
      tracheal allografts, a model of obliterative bronchiolitis after lung 
      transplantation, is immunologically mediated. Whether tolerance induction by the 
      administration of anti-CD40 ligand monoclonal anti-body (MR-1) alone or in 
      conjunction with donor-derived bone marrow cells (BMCs) can prevent the 
      development of OAD was tested in this study. METHODS: BALB/c tracheal allografts 
      were heterotopically transplanted into C57BL/6 recipients. Group 1 received no 
      treatment. Group 2 received multiple infusions of donor BMCs intravenously. Group 
      3 was administered MR-1 intraperitoneally. Group 4 received donor BMCs and MR-1. 
      Allografts were harvested at several time points post-transplantation and 
      examined for the development of OAD. RESULTS: Group 1 developed cellular 
      infiltration and epithelial damage by Day 15 post-transplant and OAD by Day 28, 
      evidenced by complete obliteration of the tracheal lumen. Group 2 developed OAD 
      with similar kinetics to Group 1. Group 3 had no evidence of OAD at 28 days. At 
      Days 45 to 90, moderate cellular infiltration, epithelial metaplasia, and a 
      minimal narrowing of the tracheal lumen were evident. OAD developed by Day 120. 
      Group 4 mice had patent tracheal lumens even at 120 days post-transplantation, 
      with only mild epithelial metaplasia and luminal narrowing noted. CONCLUSIONS: 
      The administration of MR-1 alone in combination with infusions of donor bone 
      marrow cells significantly attenuated the development of OAD. Tolerance-inducing 
      regimens such as this deserve further investigation in the prevention of 
      post-lung transplant obliterative bronchiolitis following human lung 
      transplantation.
FAU - Fernandez, Felix G
AU  - Fernandez FG
AD  - Department of Surgery, Washington University School of Medicine, St. Louis, 
      Missouri 63110, USA.
FAU - McKane, Brice
AU  - McKane B
FAU - Marshbank, Shawn
AU  - Marshbank S
FAU - Patterson, G Alexander
AU  - Patterson GA
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
LA  - eng
GR  - AI07163/AI/NIAID NIH HHS/United States
GR  - AI52752/AI/NIAID NIH HHS/United States
GR  - HL66452/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antibodies, Monoclonal)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Bone Marrow Transplantation/*immunology
MH  - Bronchiolitis Obliterans/*immunology
MH  - CD40 Ligand/*immunology
MH  - Chimerism
MH  - Combined Modality Therapy
MH  - Disease Models, Animal
MH  - Graft Rejection/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - T-Lymphocytes/immunology
MH  - Trachea/*transplantation
MH  - *Transplantation Tolerance/drug effects/immunology
MH  - Transplantation, Heterologous
MH  - Transplantation, Homologous
EDAT- 2005/07/05 09:00
MHDA- 2005/11/03 09:00
CRDT- 2005/07/05 09:00
PHST- 2003/12/18 00:00 [received]
PHST- 2004/05/31 00:00 [revised]
PHST- 2004/06/03 00:00 [accepted]
PHST- 2005/07/05 09:00 [pubmed]
PHST- 2005/11/03 09:00 [medline]
PHST- 2005/07/05 09:00 [entrez]
AID - S1053-2498(04)00345-6 [pii]
AID - 10.1016/j.healun.2004.06.008 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2005 Jul;24(7 Suppl):S232-8. doi: 
      10.1016/j.healun.2004.06.008.