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

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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.


Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • University of Toronto

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området


Sidor (från-till)74-84
Utgåva nummer1
StatusPublished - 2019 jul 4
Peer review utfördJa