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Amitriptyline Decreases Mouse Lung Endothelial Cell Inflammatory Responses to Packed Red Blood Cell Microparticles
Lindsey Wattley1, Ryan Chae1, Christopher Nguyen1
1Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
The Journal of Surgical Research
|October 18, 2024
Summary
Red blood cell microparticles activate lung endothelial cells, causing inflammation. Amitriptyline treatment reduced this response by inhibiting acid sphingomyelinase (ASM), suggesting a therapeutic strategy for transfusion-related lung injury.
Area of Science:
- Immunology
- Cell Biology
- Transfusion Medicine
Background:
- Packed red blood cell (pRBC) transfusion can cause lung injury.
- Red cell microparticles (MPs) may activate endothelial cells, contributing to this injury.
- Amitriptyline has shown anti-inflammatory effects in sepsis models.
Purpose of the Study:
- To investigate if red cell MPs activate lung endothelial cells.
- To determine if amitriptyline can mitigate MP-induced inflammation via acid sphingomyelinase (ASM) inhibition.
Main Methods:
- Isolated MPs from stored murine pRBCs.
- Treated mouse lung endothelial cells (MLECs) with MPs and amitriptyline.
- Assessed chemokine secretion, adhesion molecule shedding, and ASM activity.
Main Results:
- MPs increased chemokine secretion and adhesion molecule shedding in MLECs.
- Amitriptyline decreased ASM activity in MLECs exposed to MPs.
- Amitriptyline reduced MP-induced inflammation at 4 hours but not 24 hours.
Conclusions:
- Endothelial cell activation by MPs involves pro-inflammatory chemokines and adhesion molecules.
- Amitriptyline pretreatment reduces MLEC inflammatory response and ASM activity.
- ASM inhibition is a potential strategy to mitigate inflammation from red blood cell storage lesions.
