PMID- 22980951
OWN - NLM
STAT- MEDLINE
DCOM- 20130409
LR  - 20211021
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 31
IP  - 11
DP  - 2012 Nov
TI  - Complement activation is not required for obliterative airway disease induced by 
      antibodies to major histocompatibility complex class I: Implications for chronic 
      lung rejection.
PG  - 1214-22
LID - S1053-2498(12)01219-3 [pii]
LID - 10.1016/j.healun.2012.08.011 [doi]
AB  - BACKGROUND: The role of non-complement activating antibodies (ncAbs) to 
      mismatched donor human leukocyte antigen (HLA) in the pathogenesis of chronic 
      lung rejection is not known. We used a murine model of obliterative airway 
      disease (OAD) induced by Abs to major histocompatibility major histocompatibility 
      complex (MHC) class I and serum from donor-specific Abs developed in human lung 
      transplant (LTx) recipients to test the role of ncAbs in the development of OAD 
      and bronchiolitis obliterans syndrome (BOS). METHODS: Anti-MHC ncAbs were 
      administered intrabronchially in B.10 mice or in C3 knockout (C3KO) mice. Lungs 
      were analyzed by histopathology. Lymphocytes secreting interleukin (IL)-17, 
      interferon-gamma, or IL-10 to collagen V and K-alpha1 tubulin (Kalpha1T) were enumerated by 
      enzyme-linked immunospot assay. Serum antibodies to collagen V and Kalpha1T were 
      determined by enzyme-linked immunosorbent assay. Cytokine and growth factor 
      expression in lungs was determined by real-time polymerase chain reaction. 
      Donor-specific Abs from patients with BOS and control BOS-negative LTx recipients 
      were analyzed by C1q assay. RESULTS: Administration of ncAbs in B.10 mice or C3KO 
      resulted in OAD lesions. There were significant increases in IL-17- and 
      interferon-gamma-secreting cells to collagen V and Kalpha1T, along with serum Abs to 
      these antigens. There was also augmented expression of monocyte chemotactic 
      protein-1, IL-6, IL-1beta, vascular endothelial growth factor, transforming growth 
      factor-beta, and fibroblastic growth factor in mice administered ncAbs by Day 3. 
      Among 5 LTx recipients with BOS, only 1 had C1q binding donor-specific Abs. 
      CONCLUSION: Complement activation by Abs to MHC class I is not required for 
      development of OAD and human BOS. Therefore, anti-MHC binding to epithelial and 
      endothelial cells can directly activate pro-fibrotic and pro-inflammatory 
      cascades leading to immune response to self-antigens and chronic rejection.
CI  - Copyright (c) 2012 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Takenaka, Masashi
AU  - Takenaka M
AD  - Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Subramanian, Vijay
AU  - Subramanian V
FAU - Tiriveedhi, Venkataswarup
AU  - Tiriveedhi V
FAU - Phelan, Donna
AU  - Phelan D
FAU - Hachem, Ramsey
AU  - Hachem R
FAU - Trulock, Elbert
AU  - Trulock E
FAU - Gelman, Andrew E
AU  - Gelman AE
FAU - Patterson, G Alexander
AU  - Patterson GA
FAU - Hoshinaga, Kiyotaka
AU  - Hoshinaga K
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
LA  - eng
GR  - R01 HL056643/HL/NHLBI NIH HHS/United States
GR  - R01 HL092514/HL/NHLBI NIH HHS/United States
GR  - HL-092514-01A2/HL/NHLBI NIH HHS/United States
GR  - HL-056643/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120911
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)
RN  - 0 (Complement C3)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Interleukin-17)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibodies/*adverse effects/*immunology
MH  - Bronchiolitis Obliterans/etiology/*immunology
MH  - Complement Activation/*immunology
MH  - Complement C3/deficiency/genetics/metabolism
MH  - Disease Models, Animal
MH  - Graft Rejection/*immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-17/metabolism
MH  - Lung Transplantation/*immunology
MH  - Lymphocytes/metabolism
MH  - Major Histocompatibility Complex/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
PMC - PMC3472127
MID - NIHMS407386
COIS- Disclosure statement The authors have no conflicts of interest to disclose.
EDAT- 2012/09/18 06:00
MHDA- 2013/04/10 06:00
PMCR- 2013/11/01
CRDT- 2012/09/18 06:00
PHST- 2012/03/09 00:00 [received]
PHST- 2012/06/13 00:00 [revised]
PHST- 2012/08/04 00:00 [accepted]
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/04/10 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - S1053-2498(12)01219-3 [pii]
AID - 10.1016/j.healun.2012.08.011 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2012 Nov;31(11):1214-22. doi: 
      10.1016/j.healun.2012.08.011. Epub 2012 Sep 11.