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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 orcid ; 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
; ; ; and
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
2022-04-25 23:28:27
@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}},
  keywords     = {{Acute lung injury; TRALI; Osteopontin}},
  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}},
}