Daily Archives: August 15, 2017

Not typical lysosomes: Do engulfed PFC droplets migrate up the ER

Electron microgaphs of lung, Legacy Perfluorocarbons, The cell: images, Ultimate order, the cell

Looking at lysosomes in the lung of mice which have breathed perfluorochemical (PFC) liquids is interesting. These are old archived micrographs from the early 1970s but have a lot of valuable information about the reactivity of perfluorochemicals in the body (the latter being touted as totally inert.  Regardless of what science says about the reactivity of PFC they do cause a mountain of effects in humans, not the least of which is an immediate uptake by the reticuloendothelial system, massive sequestering and dumping of enzymes into the resultant lysosomes, and a kind of partitioning, or re-partitioning, or re-emulsification of the PFC, depending upon whether it was breated as a neat liquid, or infused as an emulsion with other agents accompanying it.

So “case in point” is this alveolar macrophage, picture taken from the lung of a mouse which breathed E2 for 3 hours and was allowed to recover for 48 hours then lungs taken for electron microscopy (and probably chemical analysis, though I have no clue where those data are at this point 40 years down the pike).  I just know that my negative number is 1351, and that block number is 4840, magnification was 5,000 (Zeiss 10) date 2 17 1975 at 60kv.  Mouse weighed 16.85g, breathed E2 for 3 hours on 2 3 1975, and was processed on 2 5 1975, which equates to 48 hour recovery. The sample of lung was taken from the R, mid lobe.

The image below (L) is a portion of the original negative (scanned as a transparency from the film) with an enlargement (box demarcates it) on the right where I have “pseudocolored” the protein densities with purple, which surround the empty footprints where the PFC was fixed (leaving the nice round spaces) in the cytoplasm. About 6 ribosomes (@27nm diameter) are also highlighted beneath the central phagolysosome?lysosome?membrane structure to show that the size of the smallest perfluorochemical droplets is in the nanometer range, before — before what, perhaps being small enough to diffuse back into the alveolar air space and be exhaled.  I don’t believe anyone knows whether the larger or the smaller E2 droplets are more apt to move into the alveolar air space.  There is one tiny droplet which is about 27 nm nesteled between two ribosomes… go figure.  The enzyme response here is pretty amazing, and appears in section to be most often seen as spheres, but is more likely to be a longer sausage shaped lumpy body.

The bottom line of this image is that these droplets appear to migrate along the membrane systems.

perfluorochemicals E2 droplets in murine alveolar macrophage

Some perfluorocarbon based blood substitute – “trivia” or not so trivial

Ultimate order, the cell

The febrile reaction to PFC based blood substitutes was purported (Donat R Spahn, Blood substitutes Artificial oxygen carriers: perfluorocarbon emulsions. Crit Care. 1999; 3(5): R93–R97) to be related to particle size of the emulsified infusion fluid. Lower particle size was stated to reduce the uptake by the reticuloendothelial system, which increased tolerability, as that stimulation of phagocytosis, and what must be (unmentioned) feedback loops, was deemed responsible for fever and flu like symptoms in patients receiving the blood substitues.

Spahn quotes statistics for IV administration of Oxygent “Intravascular half life is dose-dependent, and for Oxygent was found to be 9.4 ± 2.2 h for a dose of 1.8 g/kg [4]. After the initial uptake of the perfluorocarbon emulsion into the RES the droplets are slowly broken down, and the perfluorocarbon molecules are taken up in the blood again (bound to blood lipids) and transported to the lungs, where the unaltered perfluorocarbon molecules are finally excreted via exhalation. At present no metabolism of fluorocarbon molecules is known in humans.”

I didn’t see any micrographs which gave clue as to “break-down” of droplets, so this is confusing.  I have seen completely solid “footprints” of fluorocarbons, round and with lysosomal enzymes, sometimes a lot, surrounding or off to one side of a droplet, I have also seen the frothy huge lysosomal inclusions which do not have the orderly rounded appearance.