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Removal of activated neutrophils by a polymyxin B-immobilized fiber (PMX) column
Yohei Miyamoto1, Ayuka Suzuki1, Hiroki Otsuka2
1Toray Industries Inc, Chuo-ku, Tokyo, Japan.
Background:
Polymyxin B-immobilized fiber (PMX) columns are used to treat endotoxemic septic shock and have also been considered for the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), a condition defined by the absence of infection. Since the potential therapeutic effects beyond endotoxin adsorption remain unclear, we investigated the in vitro adsorption of various leukocyte subtypes using PMX columns under controlled stimulation.
Methods:
Whole blood from six healthy donors was treated with or without llipopolysaccharide (LPS) to model leukocyte activation. Leukocyte subsets and activation (CD11b+) were quantified by flow cytometric analysis before and after hemoperfusion through PMX or control columns. Removal capacity (%) and changes in neutrophil-to-lymphocyte ratio (NLR) were calculated.
Results:
The removal capacities of monocytes, granulocytes, and neutrophils were significantly higher with PMX column hemoperfusion than with the control column, with more pronounced effects after LPS stimulation. Lymphocyte removal was not significant. Activated CD11b+ granulocytes and neutrophils were preferentially removed by PMX columns. NLR was significantly reduced only by PMX columns, and the rate of change in NLR correlated with neutrophil removal, with a higher coefficient of determination in LPS-treated blood.
Conclusions:
PMX columns preferentially removed activated granulocytes/neutrophils and reduced NLR in vitro. These findings provide hypothesis-generating mechanistic insights into how PMX may modulate activated leukocyte profiles beyond endotoxin adsorption.
Insights
Polymyxin B-immobilized fiber (PMX) columns effectively remove activated neutrophils and granulocytes from blood in vitro, significantly reducing the neutrophil-to-lymphocyte ratio (NLR). This suggests PMX may offer therapeutic benefits beyond endotoxin removal.
Area of Science:
- Biomedical Engineering
- Immunology
- Critical Care Medicine
Background:
- Polymyxin B-immobilized fiber (PMX) columns are established treatments for endotoxemic septic shock.
- Their efficacy in non-infectious conditions like acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is being explored.
- The mechanisms of action beyond endotoxin adsorption require further investigation.
Purpose of the Study:
- To investigate the in vitro adsorption of leukocyte subtypes by PMX columns.
- To assess the impact of PMX hemoperfusion on leukocyte activation and the neutrophil-to-lymphocyte ratio (NLR).
- To explore potential therapeutic mechanisms of PMX beyond endotoxin removal.
Main Methods:
- Whole blood from healthy donors was subjected to hemoperfusion through PMX or control columns.
- Lipopolysaccharide (LPS) was used to stimulate leukocyte activation.
- Leukocyte subsets and activation markers (CD11b+) were quantified using flow cytometry.
- Removal capacities and changes in NLR were calculated.
Main Results:
- PMX columns demonstrated significantly higher removal capacities for monocytes, granulocytes, and neutrophils compared to control columns.
- Activated granulocytes and neutrophils were preferentially removed by PMX columns, especially after LPS stimulation.
- PMX columns significantly reduced the NLR, with a strong correlation between neutrophil removal and NLR reduction.
Conclusions:
- PMX columns preferentially adsorb activated granulocytes and neutrophils in vitro.
- PMX hemoperfusion leads to a significant reduction in NLR.
- These findings suggest PMX may modulate immune cell profiles, offering potential therapeutic benefits in inflammatory conditions beyond sepsis.
