| Innate immune activation potentiates alloimmune lung disease independent of chemokine (C-X-C motif) receptor 3. | |
| | |
MedLine Citation:
|
PMID: 21444213 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplant (HCT) and allograft rejection after lung transplant are parallel immunologic processes that lead to significant morbidity and mortality. Our murine model of pulmonary GVHD after inhaled lipopolysaccharide (LPS) suggests that innate immune activation potentiates pulmonary transplant-related alloimmunity. We hypothesized that the chemokine (C-X-C motif) receptor 3 (CXCR3) receptor is necessary for the development of LPS-induced pulmonary GVHD. METHODS: Recipient mice underwent allogeneic or syngeneic HCT, followed by inhaled LPS. CXCR3 inhibition was performed by using CXCR3-knockout donors or by systemic anti-CXCR3 antibody blockade. Pulmonary histopathology, cellular sub-populations, cytokine proteins, and transcripts were analyzed. RESULTS: Compared with the lungs of LPS-unexposed and syngeneic controls, lungs of LPS-exposed allogeneic HCT mice demonstrated prominent lymphocytic peri-vascular and peri-bronchiolar infiltrates. This pathology was associated with increased CD4(+) and CD8(+) T cells as well as an increase in CXCR3 expression on T cells, a 2-fold upregulation of CXCR3 transcript, and a 4-fold increase in its ligand CXCL10/Interferon gamma-induced protein 10 kDa (IP-10). CXCR3 inhibition using gene-knockout strategy or antibody blockade did not change the severity of pulmonary pathology, with a mean pathology score of 6.5 for sufficient vs 6.5 for knockout (p = 1.00) and a mean score of 6.8 for antibody blockade vs 7.4 for control (p = 0.46). CXCR3 inhibition did not prevent CD3 infiltration or prevent production of interleukin-12p40 or significantly change other Th1, Th2, or Th17 cytokines in the lung. CONCLUSIONS: In the setting of allogeneic HCT, innate immune activation by LPS potentiates pulmonary GVHD through CXCR3-independent mechanisms. Clinical strategies focused on inhibition of CXCR3 may prove insufficient to ameliorate transplant-related lung disease. |
| | |
Authors:
|
Tereza Martinu; Christine V Kinnier; Kymberly M Gowdy; Francine L Kelly; Laurie D Snyder; Dianhua Jiang; W Michael Foster; Stavros Garantziotis; John A Belperio; Paul W Noble; Scott M Palmer |
Related Documents
:
|
9845293 - Distribution of a beta-associated proteins in cerebrovascular amyloid of alzheimer's di... 6357303 - Immune complexes and human neoplasia. i. 14755203 - Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunct... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-27 |
Journal Detail:
|
Title: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Volume: 30 ISSN: 1557-3117 ISO Abbreviation: J. Heart Lung Transplant. Publication Date: 2011 Jun |
Date Detail:
|
Created Date: 2011-05-10 Completed Date: 2011-08-26 Revised Date: 2012-05-10 |
Medline Journal Info:
|
Nlm Unique ID: 9102703 Medline TA: J Heart Lung Transplant Country: United States |
Other Details:
|
Languages: eng Pagination: 717-25 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. tereza.martinu@duke.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Disease Models, Animal Graft vs Host Disease / chemically induced, pathology* Hematopoietic Stem Cell Transplantation Immunity, Innate / immunology* Lipopolysaccharides Lung Diseases / chemically induced, pathology* Lung Transplantation / immunology* Male Mice Mice, Inbred C57BL Mice, Knockout Receptors, CXCR3 / physiology* T-Lymphocytes / immunology Transplantation, Homologous |
| Grant Support | |
ID/Acronym/Agency:
|
1 K24 HL91140-01A2/HL/NHLBI NIH HHS; 1F32HL090265-01/HL/NHLBI NIH HHS; 1P50-HL084917-01/HL/NHLBI NIH HHS; K24 HL091140/HL/NHLBI NIH HHS; K24 HL091140-01A1/HL/NHLBI NIH HHS; K24 HL091140-04/HL/NHLBI NIH HHS; P50 HL084917-01/HL/NHLBI NIH HHS; R01 AI052201-10/AI/NIAID NIH HHS; R01 HL077291-08/HL/NHLBI NIH HHS; RR024 127-03/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Lipopolysaccharides; 0/Receptors, CXCR3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pandemic 2009 H1N1 influenza virus vaccination in lung transplant recipients: coverage, safety and c...
Next Document: False recognition in women with a history of childhood emotional neglect and diagnose of recurrent m...