Re: PKH26 and alternative live/dead stains

From: Dennis Broud 301-827-5246 FAX 301-594-6289 (BROUDD@CDER.FDA.GOV)
Date: Wed Jan 13 1999 - 14:52:11 EST


In response to Howard Shapiro's comments about PHK26

The usefulness of PKH26 depends on your instrument setup.  On the standard
Facscan/FacSort (and FacsCaliber, I believe) filter setups, PKH26 will give
you a very strong signal in both the FL2 and FL3 Channel.  If you have a very,
very bright flourochrome on your FL3 antibody, you may be able to run high
enough compensation to remove the PHK26 signal from your FL3 PMT.  I was only
able to do this once using PerCP CD45 in conjunction with PKH26 labelled Human
PBMC's.  Seems to me like the compensation was something like 78% or greater
to remove the PKH26 signal from the FL3 channel and see the remaining PerCP
signal.  For all practical purposes on the BD instruments mentioned above,
PKH26 makes your instrument into a 2 flourescent channel instrument-- FL1 for
FITC, and FL2 and FL3 for PKH26.  The PKH26 signal will easily reach the 4th
decade on these instruments in both FL2 and FL3.  BUT as an added benefit,
PKH26 is initially bright enough to be visible on a regular light microscope
at high magnification.  You can actually see little pink dots of the dye in
the cell membrane.  ALSO PKH26 is visible under flourescent microscopes for up
to 42 days after implantation in spleen tissue in models like the SCID-HU-PBL
mouse model using frozen sections.  The standard setup for Phycoerythrin will
work very nicely on most flourescent microscopes for PKH26.  REMEMBER this dye
is ALCOHOL soluble!!!! Do not submit tissue specimens for standard H and E
staining and expect to see the PKH26 in the tissues.  The dehydration process
in H and E staining uses alcohol, which will remove the PKH26 from your
sections.

  Labelling with PKH26 is not very complicated, but you do need to do a
titration with the cells of interest to establish the proper concentration for
labelling each cell line. A simple grid staining process and about 2 hours
time will establish this for you.  Once you have the concentration needed for
the cells in question, I have labelled up to 5 x 10 to the ninth Human PBMC's
in less that 2 hours for implantation into SCID mice.

Unless you are really interested in tracking the doubling time for the cells
I'd not recommend that you use PKH26.  The labelling process involves some
contact with ethanol, and you will change the permeability of your cell
membranes as you do this.  For example, immediately after staining with PKH26,
all your cells may accept Trypan Blue and give you a very dim blue color as
though they might be about to crump (die).  In the labelling process you will
also lose somewhere between 20 to 50% of your cell numbers due to
centrifugations and plain old cell death. Some of this comes from having to
put the cells into a system that is free of exogenous protein during the
staining process. You will probably get a nice little snotty clumping of some
cells that are dying.  (You gene jockeys will know what I mean--its like a
little snotty DNA clot) BUT--The PKH26 stained cells that survive are,
however, quite viable, and based on studies with human PBMC's and CEM cells in
tissue culture, have somewhat faster doubling times for the first few
generations when compared with cells from the same donor that are not labelled
with PKH26.  Whether this is due to stimulation or increased permeability I do
not know.

Dennis Broud, Microbiologist
DAPR,OTR, OPS, FDA
HFD-910, MOD1, Room 3307
8301 Muirkirk Road
Laurel, MD 20708
Phone (301) 594-5879

The comments above are the author's own, and do not in anyway reflect an
official position by the US Food and Drug Administration or the United States
Government.



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