Re: PMN isolation w/o activation

From: Scott I. Simon (sisimon@UCDAVIS.EDU)
Date: Tue Dec 03 2002 - 13:28:20 EST


Hi Keith;
We have published a few papers on whole blood analysis of PMN function. The 
first was:

Simon, S.I., Chambers, D.C., Butcher, E., Sklar, L.A. (1992) Neutrophil 
aggregation is b2 Integrin and L-selectin dependent in blood and isolated 
cells as measured by flow cytometry. J.Immun. 149:2765-2771.

&

Kostantinos Konstantopoulos,  Neelamegham S., Burns, A.R. Kansas, G.S., 
Snapp, K.R., Berg. E.L., Hellums, J.D., McIntire, L.V., Simon, S.I., (1998) 
Venous levels of shear induce neutrophil-platelet and neutrophil 
aggregation in blood via P-selectin and ß2integrin. Circulation 98: 873-882.
Hope this helps
Scott Simon





At 09:24 AM 11/27/02 +0100, Keith Thompson wrote:

>Thanks for the information. Sorry to trouble you more, but do you have
>details or a reference to the 'whole blood system'?
>
>Dr K.Thompson
>
>IMMI
>Oslo
>Norway
>
>----- Original Message -----
>From: "Arnold Richard Pizzey" <a.pizzey@ucl.ac.uk>
>To: cyto-inbox
>Sent: Tuesday, November 26, 2002 12:20 PM
>Subject: PMN isolation w/o activation
>
>
>
>Hello Ray,
>
>More years ago than I care to remember, I did a lot of work with PMNs
>looking at the respiratory burst as well as activation markers. Activation
>of PMNs was not usually a problem. (Although you will always get the odd
>individual donor whose PMNs are upregulated) After playing around for a
>couple of years with different schemes for Granulocyte (remember, you're
>going to get some Eosinophils in there as well unless you deplete them)
>isolation, we came up with following:
>
>Note all operations are to be carried out at room temperature only, put
>them at 37' C or on ice and they will upregulate.
>
>The assumed volume of blood is 50ml
>
>i) Take blood into EDTA.
>
>ii) Add 5ml dextran (in 0.9% NaCl) and mix very gently for about 2 minutes.
>
>iii) Draw up the above mixture into a syringe with an offset luer, taking
>care not to introduce bubbles.
>
>iv) Place the syringe *on its side* with the luer uppermost and leave for
>5mins.
>
>vi) After 5mins, sharply tap the syringe and leave for another 5mins.
>
>vii) Incline the syringe and expel the supernatent directly onto a cushion
>of equal volume Ficoll (you can do this with either a kwill filling tube on
>the end of the syringe, or a large gauge needle)
>viii) Centrifuge 400g/20mins at room temperature -a refrigerated centrifuge
>is ideal to maintain the temperature at 20'C.
>ix) Discard the supernatent by inverting the tube.
>
>x) Resuspend in Granulocyte maintenance buffer (PBS +Mg +Ca +5mM Glucose)
>
>Cells will be quite happy in this buffer at room temperature for up to
>about 4-5 hours. I have tried keeping the cells on ice, but generally they
>seem to do worse.
>
>With some practice, you can use the above cells directly -the RBC
>contamination is minimal however, if you wish, the following hypotonic
>lysis method give minimal upregulation.
>
>Note, all solutions are 0'C
>
>i) To the pellet, add 2ml Phosphate buffered saline (no Ca/Mg) and
>carefully resuspend to an homogenous mixture -avoid pipetting up and down-
>you can examine the cells at this point to ensure that there are no
>aggregates.
>
>ii) Add 5ml H20 and gently rock the tube for 45 seconds.
>
>iii) Add 2ml 3.6% Saline.
>
>iv) Add 40ml PBS (no Mg/Ca.
>
>v) Centrifuge 200g 10mins at room temp.
>
>vi) Resuspend in maintenance buffer (see above)
>
>
>Has your investigator considered moving to a whole blood system? -this
>might be seen as a step closer to the physiological state. We did quite a
>lot of work in this system using DCF as the output signal. (although there
>are better compounds now) -You can stop the burst by addition of 5mM final
>Conc. NEM then lyse the red cells with immunoprep (Beckman-Coulter) By the
>by, if you are going to use receptor-mediated activation (say fmlp) you
>will see **none** as there appears to be an inhibitory factor in plasma
>which can only be overcome by priming the cells with something like GM-CSF.
>
>Best regards,
>
>Arnold
>
>
>On 15 Nov 2002, at 15:25, ray hester wrote:
>
> >
> > An investigator here is comparing the effects of activated [using phorbol]
> > vs non-activated human PMN, but whereas they expected (based on other
> > studies) the activated PMN to have an enhancing effect compared to the
> > unactivated PMN, they find similar results from the addition of either
> > population.
> >
> > Their PMN isolation procedure involves dilution of blood 1:2 with saline,
> > addition of dextrin to 5%, allowing cells to settle for 45 min at 37 C,
> > taking the supernate and underlaying it with Histopaque, and centrifuging
> > for 30 min (I don't know the rpm).  The PMN are recovered as the pellet.
>[I
> > believe I've described this accurately]
> >
> > The markers they are looking at, on human red blood cells, are percentages
> > of RBC expressing CD36, CD49, and phosphatidyl serine.  The activated PMN
> > were expected to increase these values compared to unactivated, i.e., non
> > PMA treated, PMN, when incubated with the RBC.
> >
> > Would the isolation procedure described above be expected to activate PMN
> > without the addition of PMA?
> >
> > If so, does anyone know of a gentler isolation procedure which might
> > not/does not activate PMN?
> >
> > Thanks for any thoughts.
> >
> > Ray
> >
> > Ray Hester
> > Univ. of South Alabama
> > Mobile, AL 36688
> > rhester@jaguar1.usouthal.edu
>
>
>_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/
>Arnold Richard Pizzey
>Department of Haematology
>Royal Free and University College London Medical School
>98 Chenies Mews
>London WC1E 6HX
>U.K
>
>voice: +44 020-7679-6234
>Fax: +44 020-7679-6222
>email: a.pizzey@ucl.ac.uk
>_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/

Scott I Simon, Ph.D.
Professor of Biomedical Engineering
University of California, Davis
One Shields Avenue
1025 Academic Surge
Davis, CA 95616-5294
530-752-0299 Office
530-752-1430 Lab
530-754-5739 Fax
530-759-4380 Pager
sisimon@ucdavis.edu
http://www.bme.ucdavis.edu/faculty/ScottISimon.html



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