Osteopontin mediates murine transfusion-related acute lung injury through stimulation of pulmonary neutrophil accumulation.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8babeeb9-799a-4602-9eed-15bb371cf150
- author
- Kapur, Rick LU ; Kasetty, Gopinath LU ; Rebetz, Johan LU ; Egesten, Arne LU and Semple, John W LU
- organization
- publishing date
- 2019-07-04
- 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}}, }