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Discussion and considerations for the excretion mechanism of perfluorochemical emulsion
Y Tsuda1, K Yamanouchi, K Yokoyama
1Research Division, Green Cross Corporation, Hirakata, Japan.
Abstract:
It has been assumed that a mononuclear phagocyte system is related to the excretion of PFC emulsions: PFC particles are phagocytized by blood monocytes to be expelled through the lung alveoli. This monocyte-related mechanism may well explain excretion at an early stage when PFC particles are abundant in the blood stream. It does not, however, fully explain the manner by which PFC cells are released from the RES cells into the blood stream and into the adipose tissue. To explain this, the following mechanism has been proposed and discussed based on some experimental results. PFC emulsion particles taken up by the RES organs, are stripped at their surfactant layers in the cells and move across the cell membranes to the blood vessels and into other tissues such as adipose, at a rate that depends on the lipophilicity of the PFC's. In the blood stream, PFCs are delivered by lipoproteins to the lung and excreted into the expired air. Pharmacokinetical analysis with a compartmental model for the excretion also supported this proposed mechanism.
Insights
The reticuloendothelial system (RES) processes perfluorocarbon (PFC) emulsions, facilitating their excretion via the lungs. This study proposes a novel mechanism for PFC release from RES cells and transport to tissues.
Area of Science:
- Biomedical Science
- Pharmacokinetics
- Cell Biology
Background:
- The mononuclear phagocyte system (reticuloendothelial system, RES) is implicated in perfluorocarbon (PFC) emulsion excretion.
- Existing models explain early-stage PFC excretion via monocytes and lung alveoli.
Purpose of the Study:
- To elucidate the mechanism of PFC release from RES cells into circulation and tissues.
- To explain PFC transport to adipose tissue and subsequent excretion.
Main Methods:
- Experimental analysis of PFC emulsion uptake and processing by RES organs.
- Investigation of PFC particle behavior within cells and across membranes.
- Pharmacokinetic modeling to analyze excretion patterns.
Main Results:
- PFC particles are stripped of surfactant layers within RES cells.
- PFCs cross cell membranes and enter blood vessels and tissues like adipose tissue, influenced by lipophilicity.
- Lipoprotein-mediated transport delivers PFCs to the lungs for excretion.
Conclusions:
- A new mechanism details PFC release from RES cells, involving surfactant stripping and membrane crossing.
- PFC excretion is a multi-step process involving cellular processing, tissue distribution, and lung elimination.
- Pharmacokinetic data supports the proposed PFC excretion pathway.