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Osteopontin mediates murine transfusion-related acute lung injury through stimulation of pulmonary neutrophil accumulation.

Kapur, Rick LU ; Kasetty, Gopinath LU ; Rebetz, Johan LU ; Egesten, Arne LU and Semple, John W LU (2019) In Blood 134(1). p.74-84
Abstract
Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within 6 hours of a blood transfusion. There are no specific therapies available and the pathogenesis remains unclear. Pre-existing inflammation is a risk factor for TRALI and neutrophils (PMNs) are considered to be the major pathogenic cells mediating lung damage. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration and can function as a PMN-chemoattractant. We investigated whether OPN is involved in TRALI-induction by promoting PMN-recruitment to the... (More)
Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within 6 hours of a blood transfusion. There are no specific therapies available and the pathogenesis remains unclear. Pre-existing inflammation is a risk factor for TRALI and neutrophils (PMNs) are considered to be the major pathogenic cells mediating lung damage. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration and can function as a PMN-chemoattractant. We investigated whether OPN is involved in TRALI-induction by promoting PMN-recruitment to the lungs. Using a previously established murine TRALI model, we found that in contrast to wildtype (WT) mice, OPN knock-out (KO) mice were resistant to antibody-mediated PMN-dependent TRALI induction. Administration of purified OPN to the OPN KO mice, however, restored the TRALI response and pulmonary PMN-accumulation. Alternatively, blockade of OPN in WT mice using an anti-OPN antibody prevented the onset of TRALI induction. Using pulmonary immunohistochemistry, OPN could be specifically detected in the lungs of mice that suffered from TRALI. The OPN-mediated TRALI responses were independent from other PMN-chemoattractants including macrophage inflammatory protein (MIP)-2. These data indicate that OPN is critically required for induction of antibody-mediated murine TRALI through localization to the lungs and stimulation of pulmonary PMN-recruitment. This suggests that anti-OPN antibody-therapy may be a potential strategy to explore in targeting TRALI in patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute lung injury, TRALI, Osteopontin
in
Blood
volume
134
issue
1
pages
74 - 84
publisher
American Society of Hematology
external identifiers
  • scopus:85069270468
  • pmid:31076444
ISSN
1528-0020
DOI
10.1182/blood.2019000972
language
English
LU publication?
yes
id
8babeeb9-799a-4602-9eed-15bb371cf150
date added to LUP
2019-05-15 10:34:29
date last changed
2020-07-08 04:51:24
@article{8babeeb9-799a-4602-9eed-15bb371cf150,
  abstract     = {Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within 6 hours of a blood transfusion. There are no specific therapies available and the pathogenesis remains unclear. Pre-existing inflammation is a risk factor for TRALI and neutrophils (PMNs) are considered to be the major pathogenic cells mediating lung damage. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration and can function as a PMN-chemoattractant. We investigated whether OPN is involved in TRALI-induction by promoting PMN-recruitment to the lungs. Using a previously established murine TRALI model, we found that in contrast to wildtype (WT) mice, OPN knock-out (KO) mice were resistant to antibody-mediated PMN-dependent TRALI induction. Administration of purified OPN to the OPN KO mice, however, restored the TRALI response and pulmonary PMN-accumulation. Alternatively, blockade of OPN in WT mice using an anti-OPN antibody prevented the onset of TRALI induction. Using pulmonary immunohistochemistry, OPN could be specifically detected in the lungs of mice that suffered from TRALI. The OPN-mediated TRALI responses were independent from other PMN-chemoattractants including macrophage inflammatory protein (MIP)-2. These data indicate that OPN is critically required for induction of antibody-mediated murine TRALI through localization to the lungs and stimulation of pulmonary PMN-recruitment. This suggests that anti-OPN antibody-therapy may be a potential strategy to explore in targeting TRALI in patients. },
  author       = {Kapur, Rick and Kasetty, Gopinath and Rebetz, Johan and Egesten, Arne and Semple, John W},
  issn         = {1528-0020},
  language     = {eng},
  month        = {07},
  number       = {1},
  pages        = {74--84},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Osteopontin mediates murine transfusion-related acute lung injury through stimulation of pulmonary neutrophil accumulation.},
  url          = {http://dx.doi.org/10.1182/blood.2019000972},
  doi          = {10.1182/blood.2019000972},
  volume       = {134},
  year         = {2019},
}