Re: A little more on CFSE

From: Adrian Smith (A.Smith@centenary.usyd.edu.AU)
Date: Thu Feb 24 2000 - 20:39:56 EST


>Hi, I thought that since there was so much interest in CFSE I would
>share my recent experiences. I hope it will be of some use.
>
>I have been labelling human PBMC with CFSE according to Current
>Protocols methodology. After labelling, my cells were more than 95%
>viable by trypan blue exclusion... but would not proliferate in culture.
>In the end, by titration, I found that reducing the final concentration
>of CFSE to 2 micromolar, (instead of the suggested 10 micromolar) gave
>good staining while still allowing good proliferation.
>
>So the moral of the story seems to be that CSFE can do funny things to
>cells, and although they are viable they may not be fully functional!
>
>
>--
>Lisa M Gale
>Department of Microbiology & Immunology
>University of Adelaide
>ph  +61 8 8303 4630
>fax  +61 8 8303 4362
>email lisa.gale@adelaide.edu.au




Yes, it always pays to be careful. People have noted effects of CFSE
on cells as far back as 1994 (at least that was the earliest
publication I could find)...



for example...

>De Clerck, L. S., et al. (1994) Use of fluorescent dyes in the
>determination of adherence of human leucocytes to endothelial cells
>and the effect of fluorochromes on cellular function. Journal of
>Immunological Methods 172(1): 115-24.
>A number of supravital fluorochromes are available to study
>leucocyte functions in vitro and in vivo. The fluorescein ester most
>widely used, fluorescein diacetate, has the disadvantage of rapid
>cellular efflux, whereas more recently developed fluorescent probes
>do not exhibit this inconvenient trait. However, their effect on
>cellular functions has not been thoroughly investigated in humans.
>In this study, we describe a simple and rapid fluorometric method
>for measuring cell adhesion to endothelium, comparing 5 different
>fluorochromes. Furthermore, we evaluated the effect of fluorescent
>dye labelling (with CFDA, CFSE, BCECF-AM, calcein-AM or DiI), on
>various cell functions, including, apart from adhesion, lymphocyte
>proliferation, granulocyte chemotaxis and superoxide production.
>calcein-AM and DiI proved to be the fluorochromes with the least
>effect on cellular function. BCECF-AM did not interfere with
>lymphocyte proliferation, but exhibited some influence on superoxide
>production and chemotaxis of granulocytes. CFDA showed a detrimental
>effect on both lymphocyte and granulocyte functions whereas CFSE
>gave intermediate results. In the adhesion assay, calcein-AM, CFSE
>and DiI performed comparably well. Since labelling with C12-DiI was
>homogeneous, this probe was also appropriate for the adhesion test,
>although somewhat higher background staining was present. We
>conclude that the fluorochromes are powerful tools when analysing
>the adhesion of human leucocytes to endothelial cells. However,
>since fluorochrome labelling can interfere with other cellular
>functions, the fluorescent probe has to be carefully chosen with
>regard to the cell type and function to be studied.

  (NOTE: I haven't heard of CFSE affecting murine cells in the same
way. Anyone?)



Adrian Smith

******************************************************
Adrian Smith (PhD Student)        T CELL BIOLOGY GROUP
Centenary Institute of Cancer Medicine & Cell Biology
Locked Bag No.6 Newtown, NSW 2042 AUSTRALIA.
******************************************************



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