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Microparticles in red cell concentrates prime polymorphonuclear neutrophils and cause acute lung injury in a
Rufeng Xie1, Yiming Yang1, Yueyue Zhu2
1Shanghai Institute of Blood Transfusion, Shanghai Blood Center, Shanghai, China.
Abstract:
Red cell-derived microparticles (RMPs) are potential mediators of transfusion-related acute lung injury (TRALI). The aim of this study was to investigate the effects of microparticles present in red cell concentrates (RCC) on polymorphonuclear neutrophil (PMN) respiratory burst and acute lung injury (ALI) in mice. Microparticles (MPs) in RCC supernatant were quantified using flow cytometry. The priming activity of either isolated MPs or RCC supernatant toward human PMN was measured in vitro. Mice were injected with lipopolysaccharide (LPS), followed by an infusion of either isolated MPs or heat-treated RCC supernatant. The lungs were harvested to assess myeloperoxidase (MPO) activity, histology and pulmonary edema. Protein content in bronchoalveolar lavage fluid (BALF) was measured. The number of RMPs increased significantly during storage. Both isolated MPs and the supernatants from RCCs that had been stored for 28 and 35days effectively primed the PMN respiratory burst. The infusion of isolated MPs or supernatants that had been stored for >28days into LPS-treated mice caused ALI. The filtered supernatant resulted in significantly ameliorated mouse ALI. MPs that accumulate during RCC storage prime the PMN respiratory burst and cause ALI in a two-event mouse model.
Insights
Red cell-derived microparticles (RMPs) accumulating during red cell concentrate (RCC) storage prime neutrophils. This priming can lead to transfusion-related acute lung injury (TRALI) in a mouse model.
Area of Science:
- Hematology
- Immunology
- Pulmonary Medicine
Background:
- Red cell-derived microparticles (RMPs) are implicated in transfusion-related acute lung injury (TRALI).
- The role of microparticles (MPs) in stored red blood cells (RBCs) concerning acute lung injury (ALI) requires further elucidation.
Purpose of the Study:
- To investigate the impact of microparticles in red cell concentrates (RCCs) on neutrophil respiratory burst and ALI in mice.
- To determine if MPs accumulating during RCC storage contribute to ALI pathogenesis.
Main Methods:
- Quantified MPs in RCC supernatant using flow cytometry.
- Assessed in vitro priming of human polymorphonuclear neutrophils (PMNs) by isolated MPs and RCC supernatant.
- Induced ALI in mice using lipopolysaccharide (LPS) followed by MP or RCC supernatant infusion.
- Evaluated lung injury markers including myeloperoxidase (MPO) activity, histology, and pulmonary edema.
Main Results:
- RMP numbers significantly increased with RCC storage duration.
- MPs and RCC supernatants from stored units (>28 days) effectively primed PMN respiratory burst.
- Infusion of MPs or aged RCC supernatant induced ALI in LPS-treated mice.
- Filtered supernatant significantly reduced ALI severity, indicating MPs are key mediators.
Conclusions:
- Accumulation of RMPs during RCC storage enhances PMN activation.
- RMPs are critical mediators contributing to the development of ALI in a two-event model.
- Storage duration of RCCs influences the risk of transfusion-related lung injury.
