RE: Apoptosis light scatter detection

From: Dr Mark W Lowdell (m.lowdell@rfc.ucl.ac.uk)
Date: Fri Jun 14 2002 - 03:50:17 EST


Caroline Dive published an excellent paper on this subject in Bioch
Biophys Acta in 1993 and I have always believed that the FSC changes
detected in early apoptosis (decreasing FSC signal) are due to increased
refractive index of the cell membrane and thus cells which are swelling
give lower FSC.  I've taken this as "fact" having heard it from a number
of sources but I'd be grateful for an up date from the current experts.
When teaching "flow" I always use this as an example of when FSC doesn't
necessarily relate to cell size.
Regards

Dr Mark W Lowdell
Senior Lecturer in Haematology /
Head of Laboratory of Cellular Therapeutics
RFUCMS

T - 020 7830 2183
F - 020 7794 0645


-----Original Message-----
From: Zucker.Robert@EPAMAIL.EPA.GOV
[mailto:Zucker.Robert@EPAMAIL.EPA.GOV]
Sent: 13 June 2002 05:44
To: cyto-inbox
Subject: Apoptosis light scatter detection



At a recent lecture on apoptosis, the hypothesis was put fourth that
cell volume accompanied by ion changes were the very significant and
initial events during apoptosis in lymphoid cells. It was suggested that
these changes came prior to caspase changes, mitochondrial changes,
membrane potential changes and nuclear fragmentation.

1. What is the current thinking regarding the sequential events in the
apoptosis process that can be detected by fluorescent-based assays like
flow cytometry?

2. After the lecture, I asked the speaker the question regarding the
capability of a flow cytometer to detect early size changes using light
scatter. Does the flow cytometer have a sufficient sensitivity to
measure early volume changes by light scatter?  What is the percentage
decrease in cellular volume that would be necessary to effectively make
the conclusion that cell volume size changes are the initial event in
the apoptosis pathway?  The speaker did not think this was a relevant
question and felt it was only a technical question in which the operator
of the equipment could easily answer. In my opinion in order to prove
the hypothesis that cell volume is indeed an initial event in the
apoptosis pathway, one has to understand how effective the flow
cytometer will be in determining early size changes using the light
scatter parameters. Can small changes in light scatter be detected early
in the apoptosis process and thus be used as an initial measurable flow
cyotmetric event in the apoptosis pathway? Bob


Robert M. Zucker, PhD
U.S. Environmental Protection Agency
Office of Research and Development
National Health and Environmental Effects Research Laboratory
Reproductive Toxicology Division, MD 72 Research Triangle Park, North
Carolina, 27711
Tel: 919-541-1585; fax 919-541-4017
e-mail: zucker.robert@epa.gov



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