Pulmonary endothelial permeability is increased by fluid from packed red blood cell units but not by fluid from clinically-available washed units

Abstract

Background: Massive transfusions are a risk factor for acute respiratory distress syndrome (ARDS) in severely injured patients. Neutrophil priming has been proposed to be an integral part of the early inflammatory response to trauma. To complement that work, we studied another major cell type involved in inflammation: the endothelial cell. Our hypothesis was that soluble factors from units of leukoreduced packed red blood cells (PRBC) directly increase pulmonary endothelial permeability. We also determined whether fluid from clinically-available washed PRBC units affects endothelial permeability.

Methods: As a measure of permeability, transendothelial electrical resistance (TER) was determined across monolayers of a human pulmonary microvascular endothelial cell line after addition of full-strength, diluted, and washed PRBC fluid. Monolayers were stained with phalloidin to assess intercellular space. Storage solution Adsol-1 was tested alone to determine additive component effects on TER.

Results: PRBC fluid decreased TER and increased intercellular space, both of which indicate an increase in endothelial monolayer permeability. PRBC fluid diluted to 2% and washed PRBC fluid did not decrease TER and thereby did not change endothelial permeability. Likewise, Adsol-1 did not duplicate the dramatic decrease in TER seen with the PRBC fluid.

Conclusions: Fluid from stored PRBC units contains a soluble, transferable factor that directly increases endothelial permeability. Fluid from washed PRBC units, currently available for patients with immunoglobulin A allergies, does not. This study complements previous work of others that demonstrated that neutrophil priming by PRBC fluid is abrogated by washing. Now that two cell types have been shown to respond more favorably to washed PRBC in vitro, clinical studies should be initiated to investigate whether use of washed PRBC reduces ARDS following transfusions in trauma patients.