35. Glen Frey and Neutrophilic Granulocytic White Blood Cells (WBC) – Neutrophils

Glen Frey Montage

Glen Frey and the Eagles – early days, 1977, Playing Lying Eyes and Hotel California at The Capital Centre, LA.

Accessed at http://edition.cnn.com/2016/01/19/entertainment/glenn-frey-songs-eagles-hotel-california-feat/index.html on 20 January 2016.

What on earth is happening to us baby-boomers (1946-1966)? First it was David Bowie, then Alan Rickman (both died because of cancer) and now another of my musical heroes, Glen Frey, of my favourite Country-Rock band- the Eagles, kicks the bucket, all three of them in the space of less than two weeks. At least Glen Frey’s death was not attributable to cancer; now that would have been even scarier, given my present predicament. What do you think?   We are devastated. We have seen the Eagles, albeit in later years, 2007, at Hampden Park, Glasgow (and a long way from the stage), but also 2014, at the 02 arena in Leeds (and thankfully much closer to the stage, but also with better nay, fantastic acoustics!).

Thank goodness for those stage screens – in Glasgow, but curses on them – in Leeds, where they acted as a complete distraction when not required on that occasion. I suppose the cheap seats still needed them, but one gets fairly picky having splashed out for posh seats!  The Eagles’ Leeds concert was preceded by our visit the previous night to the same venue to experience Dolly Parton (also our second viewing – we saw her in Belfast in 2007 too – busy year prior to migrating to New Zealand in September). She was brilliant on both visits but a problem with the PA system for the first half of the concert in Leeds spoilt things even though Dolly added repeat performances of a couple “first half songs” in the second part of the show. No worries we thought, still have the Eagles to come tomorrow, and we were more than compensated!

Eagles

A later version of the Eagles.

Alan Rickman as the Sherriff of Nottingham in my favourite role of his:

Accessed at http://www.telegraph.co.uk/news/celebritynews/12099543/Alan-rickman-dead-at-69-latest.html on 20 January 2016.

Alan Rickman Robin Hood

Yes, yet another baby-boomer, Lemmy from Motorhead, is a further casualty of cancer (prostate), though a little earlier, but not by much, than the recent spate.

Lemmy Cancer Death

Accessed at http://www.teamrock.com/news/2016-01-20/lemmy-s-cause-of-death-listed-as-prostate-cancer on 20 January 2016.

 

Dolly Parton at 70

A modern version of Dolly Parton on her 70th birthday tour.

Accessed at http://themuse.jezebel.com/happy-70th-birthday-dolly-parton-lets-celebrate-with-1753849659 on 20 January 2016.

 

Dolly Parton Little Sparrow

Dolly Parton playing “Little Sparrow” – her encore at the Leeds concert!

Accessed at http://themuse.jezebel.com/happy-70th-birthday-dolly-parton-lets-celebrate-with-1753849659 on 20 January 2016.

However, Glen did die of multiple disorders including pneumonia, and this is my link between him and those vital little buggers that circulate in our blood stream: our neutrophilic, granulocytic white blood cell (WBC) (or abbreviated to neutrophil and sometimes called Poly-Morphonuclear Neutrophil, PMN, because of their multi-lobed nucleus). These cells get their name from their appearance under a light microscope at high resolution and magnification (>500x) from a combination of their staining and the presence of distinct ‘granules’ that are in fact vesicles containing packets of chemicals (eg, hydrogen peroxide) as well as highly specific enzymes that assist in the killing and elimination of bacteria associated with infections such as pneumonia.

To see one of these tremendously hard-working little gems of the blood system a small drop of freshly-drawn blood is placed upon a microscope slide (or at least it was, way back when as a haematologist I prepared my own) and a thin film is created by drawing out this drop with another slide. The blood-covered slide is allowed to air dry and then it is (was) placed in a Coplin jar for staining.

Blood film or smear

 

Blood film or ‘smear’ prepared on microscope glass slides from “Making and Staining a Blood Smear”: Accessed at https://www.uvm.edu/~jschall/pdfs/techniques/bloodsmears.pdf on 20 January 2016.

Coplin is just one of the many offerings I get from word-processor auto spellcheckers for my first name – others include colon, coin, Collin, Coppin, Copland and on and on.  A Coplin jar is a small, beautifully crafted glass vessel with an accompanying lid, containing the stain, Giemsa.  Giemsa is like a combo of  Haematoxylin (Alkaline blue dye) and Eosin (Acidic red dye). The Haematoxylin-like component is attracted to alkali-loving cell structures such as Nuclear Chromatin as well as alkali-loving components found in some white blood cell granulocyte vesicles. Eosin is attracted to acid loving components, including those in WBC vesicles or ‘granules’.

The granulocytes get their name because their granules are easily visible and distinctively coloured. All three types of these WBCs mount their attack rapidly on infectious organisms or damaged cells and tissues. In fact, the three types of granulocytic WBC are not equally represented. Alphabetically, they are the acidophil, actually eosinophil (about 5-10%), the basophil (about 0.1-2.0%) and the neutrophil (about 60-90%). Clearly the neutrophil is boss in this subcategory of WBCs. The names of all three granulocyte cell types is associated with the staining of their ‘granules’ in this dye combo: under the light microscope eosinophils have bright red-orange granules; basophils have dark blue-purple, nearly black ones, and neutrophils, you’ve guessed it, have the middle ground – they appear purple-mauve-lilac (at least they did to my eye), and are thus ‘neutral’ or between blue and red. Hence the neutrophil is named, and now finally you know what I was on about in my previous cancer blog entry.

 

WBC montage

White blood cells in a stained blood film.

Top l to r: Eosinophil (Acidophil), Basophil, Neutrophil, also known as a Poly-Morphonuclear Neutrophil (PMN); Bottom l to r: Lymphocyte, Monocyte

The other category of WBCs is the non-granulocytic population comprising round or oval shaped lymphocytes and the similarly shaped but larger monocytes. These two functionally different cell types look similar to one another in the blood-stained images seen under the microscope, partly because the lymphocyte population is diverse in size and sometimes a lymphocyte is nearly as large as a monocyte. Nevertheless, they can be differentiated (distinguished). Both types have a nucleus that occupies much of the cell volume, though the monocyte nucleus often appears indented. For better financed haematology labs fortunate to have better microscopes (such as the German Leitz, or even better, a German-again Zeiss) small ‘granules’ can sometimes be seen in monocytes. Mobilisation of lymphocytes and monocytes is somewhat slower than for granulocytes, though this can depend upon whether a person has been infected previously with the same organism, and in which case these cells can respond quicker, though again usually not as rapidly as the granulocytic WBCs mount their attack.

Complicated stuff, eh?  Just to add a little more to your headache then, neutrophils often work in close collaboration with monocytes against some infectious bacteria. Monocytes are the longest lived of the WBCs. Further, after the initial attacks, predominantly by granulocytes, breakdown products released from the devastation of battle with bacteria may attract lymphocytes to the scene and it is these cells that then initiate or kick start the immune response, and it is this and subsequent reproduction of these cells that ‘prime’ and equip us to be better armed against the specific (or sometimes related) organisms. On a subsequent exposure to the infectious organism (bacteria already mentioned, but also viruses, fungi and parasites) lymphocytes particularly get to the site of action quicker than on the first infection and further, these already ‘primed’ cells receive intercellular signals that trigger cell division, and proliferation through exponential reproduction.

The total population of lymphocytes may have different activities, particularly during this ‘second exposure’ phase of the immune response. Some, the so-called B-Lymphocytes (or B cells), produce specific antibodies against the target infection whilst T-Lymphocytes (or T cells) mount direct cell attacks on the enemy. Also, some T cells form a repository of ‘helper’ cells that also assist B cells in producing more antibody as well as helping initiate cell-cell recognition. It is the T cell lymphocyte population that is gradually destroyed in Human Immunodeficiency Virus (HIV) infections and ultimtely (without treatment) leads to Acquired Immune Deficiency Syndrome (AIDS).

Returning to granulocytes, it is eosinophils that cooperate (and often fail) with neutrophils in attempting to destroy parasites, and can be often seen in great numbers in thin sections of human tissue plus parasite-infected tissues from sampled areas of the body when viewed under a light microscope by histopathologists. Basophils often appear at the site of inflammatory reactions, and may even attract eosinophils to the action as they release histamine from their ‘granules’ – and so also can be seen, though not exclusively, at the site of a particularly resistant parasitic infections.

Once again you deserve a bonus, and I guess it was a little remiss of me not to give you my favourite Bowie track, “Golden Years” after he died. So, with apologies here he is now. You also qualify on further grounds of putting up with some more biology or biomedical science stuff. So here goes:

David Bowie Montage

David Bowie, “Golden Years”,1975.

Accessed at https://www.youtube.com/watch?v=e4iKfUKBWDk on 20 January 2016

David Bowie Golden Years

 

That’s all folks. Bye for now.

Though please read below if you are an addict for punishment as well as more critical information about using blood-borne human stem cells for treatment of various cancers.  (A late addendum!)

BUGS001

Addendum

[“In addition to their distinctive cytochemical staining characteristics (Giemsa staining), blood cells can be distinguished on a gross level by their average size and granularity as measured by flow cytometry. With a flow cytometer, the optical effects of passing a single cell through a laser light beam can be measured in terms of light scattered by the cell in two directions – parallel to the beam (“forward scattering” or FSC) and perpendicular to the beam (“side scattering” or SSC). Greater FSC correlates with larger cell size while greater SSC correlates with more granularity in the cytoplasm and nucleus of a cell. A two-dimensional plot of FSC versus SSC for human blood cells, reveals that different cell types exhibit distinct average ranges of size and granularity. Thus, flow cytometry can be used to analyze and even physically isolate different blood cell populations. With a modified flow cytometer designed to detect fluorescent light stimulated by the laser beam, i.e., a fluorescence-activated cell sorter (FACS), even finer distinctions between different cell populations can be made if they have been treated with fluorescently tagged monoclonal antibodies directed against specific cell surface molecules, generically referred to as cluster of differentiation (CD) antigens.”]

Accessed at https://mcdb-webarchive.mcdb.ucsb.edu/sears/immunology/cells-organs/blood-cell-morphology.htm on 20 January 2016.

The various WBCs are not only recognised through this automated ‘differentiating’ process, but they can also be harvested by setting ‘gate’ windows around particular regions on the screen visualisation after a first run, then repeating the procedure with the ‘harvest’ button activated.  This differentation procedure mimicks the ‘old-fashioned’ WBC diff-count (differentiation count of at least a hundred cells and preferably more) on a stained blood film or smear, though using staining characteristics and morphology (colour of ‘granules’ particulaly, overall cell size, shape of nuclei and size and density of granules).   The absolute count of each WBC type is determined simply by mutiplying the Total WBC by the percentage of cell types present in each category – easy as pie, eh?

Finally, it is also possible using CD markers to distinguish lymphocyte sub-populations including all of those previously mentioned, the T cell variations, B cells and more recently a population of lymphocyte-like cells (size and morphology) called bone marrow-derived but now blood-borne stem cells. The identification and harvesting of these cells is now almost a routine procedure and has revolutionised treatment of many haematological diseases such as leukaemias and lymphomas as well as other cancers. Sometimes patients are exposed to lethal doses of radiation and then donor-harvested stem cells are given back to the recipient patient. This is a more complicated procedure than donor bone marrow transplants following total ablation of recipient marrow once again, but it carries a much lower risk of donor-versus-graft disease, where the donor bone marrow cells and their subsequent progeny, mature blood WBCs, can recognise and subsequently attempt to destroy recipient cells and tissues that are recognised as ‘foreign’. Blood-harvested stem cell transplants are costlier, certainly short term, but treatment with immuno-suppressant drugs for prolonged periods of illness is far from cheap either!  This is yet another topic for my New NHS, but not as we know it!

 

 

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