Neutrophil

“ For if in the places in question substances are present which act chemiotactically on the eosinophil leucocytes, in the course of time marked accumulation must occur, without an increase of their number in the blood. One might as well conclude from Neumann's experiment in lymphatic leukæmia, for example, where the artificial suppuration consisted only of polynuclear neutrophil cells, that the polynuclear cells were formed in the tissue, since in the blood they were present in very small percentage. ”

“ The eosinophil cells. These are characterised by a coarse, round granulation, staining deeply with acid dyes, and similar in other respects to the polynuclear neutrophils. With faint staining, a thin peripheral layer of the eosinophil granule is seen more deeply stained than the interior. The nucleus as a rule is not so deeply stained as in the polynuclear neutrophil, but otherwise in its general shape is completely similar. Both forms have in common a considerable contractility, which renders possible their emigration from the vessels, and their appearance in exudations and in pus. ”

“ Müller and Rieder should themselves have raised the obvious objection that the same holds good for the nucleus of the neutrophils. They would then have seen the fault in their theory; for according to it the most important blood preparing organ constitutes as it were, not the cradle of the blood cells, [Pg 156] but their grave. The simplest and readiest explanation, based too upon histological observation, is surely this: that the mononuclear eosinophil cells grow into polynuclear in the bone-marrow, but that the latter only reach the blood by means of their power of emigration. ”

“ The cytoplasm is relatively abundant, and contains great numbers of very fine neutrophilic granules. With Wright's stain the nucleus is bluish-purple, and the granules, reddish-lilac.
Polymorphonuclear leukocytes are formed in the bone-marrow from neutrophilic myelocytes. They constitute 60 to 75 per cent. of all the leukocytes: 3000 to 7500 per c.mm. of blood. Increase in their number practically always produces an increase in the total leukocyte count, and has already been discussed under "phagocytic leukocytosis." The leukocytes of pus, pus-corpuscles, belong almost wholly to this variety. ”

“ We must add that although in any case of medullary leukæmia each particular factor described is to be recognised, yet the manner of its appearance, its numerical relation to the others and to the total blood varies extremely. Apart from the degree of increase of the leucocytes, no one case is the same as another with regard to the other anomalies. In one case the blood bears a large-celled, mononuclear neutrophil character; in another the increase of the eosinophil cells predominates; in a third the nucleated red blood corpuscles preponderate ”

“ Bearing in mind that polynuclear neutrophil cells are developed and stored up only in the bone-marrow, that in ordinary leucocytosis only the polynuclear forms are increased in the blood-stream, it is evident that leucocytosis is purely a function of the bone-marrow, as Ehrlich has always insisted with all distinctness. ”

“ The eosinophil cells are as a rule diminished in ordinary polynuclear leucocytosis, as Ehrlich had already mentioned in his first communication. The diminution is often considerable, often indeed absolute.
A few diseases shew, besides the neutrophil leucocytosis, an increase of the eosinophils as well, as we shall describe in detail in the next section. ”

“ Through [Pg 172] insufficient mastery of the staining method, the characteristic and diagnostically decisive elements (neutrophil myelocytes for example) are frequently mistaken. A further source productive of misconceptions lies in the circumstance that the typical leukæmic condition of the blood may essentially change under the influences of intercurrent diseases. Thus the intrusion of a leucocytosis, brought about by secondary infection, is able to obliterate more or less the specific character of the blood. ”

“ Man and monkey for example have neutrophil granulation; guinea-pig and rabbit the pseudo-eosinophil granulation described by Kurloff; in birds we find two specific granulations present side by side, which both are oxyphil, and of which one is imbedded in the protoplasm in crystalline form, the other in the form of granules. ”

“ In a case of carcinoma of the bone-marrow, described by Epstein, with an anæmic constitution of the blood (nearly always present it may be mentioned in leukæmia) , there was found a marked increase of the white blood corpuscles, numerous neutrophil myelocytes and nucleated red corpuscles. Anyone holding, as Müller and Rieder do, that the number of eosinophil cells need not be considered in the diagnosis, must in this case have diagnosed myelogenic leukæmia. ”

“ Just as under certain conditions fat-cells may completely lose their contents without dying, so the bone-marrow cell, if the blood fails to yield to it the necessary substances, may occasionally be unable to produce more neutrophil granules. ”

“ Leucocytosis is now recognised to be chiefly an increase of the normal polynuclear neutrophil leucocytes; whereas myelogenic leukæmia brings elements into the blood that are abnormal. The cells here introduced are so characteristic as to render the diagnosis of leukæmia possible, even in the very rare cases where the total number of the white blood corpuscles is not to any extent increased. The best example of which we are aware is a case observed by v. Noorden, in which the proportion of white to red was only 1:200. ”

“ The nucleus stains very deeply with all dyes; the protoplasm possesses a strong attraction for most acid stains, and is unmistakeably characterised by the presence of a dense neutrophil granulation. The reaction of the protoplasm is alkaline, to a less degree however than in the lymphocytes. No free glycogen is contained in the polynuclear cells as a rule; nevertheless in certain diseases cells are always found which give a marked iodine reaction. In this manner the appearance of cells containing glycogen in diabetes was first proved. (Ehrlich, Gabritschewsky, Livierato.) ”

“ The pseudo-eosinophil granules of the mononuclear cells, of the guinea-pig for example, stain bluish-red in eosine-methylene blue after long fixing in superheated steam: in the transitional stages this admixture is gradually lost, and finally completely vanishes in the granules of the polynuclear leucocytes which stain pure red. Analogous observations may be made in the eosinophil cells of man and animals, and in the neutrophils of man. Hence it is even possible to decide whether an isolated granule belonged to an old or to a young cell. ”

“ On the grounds of this observation Ehrlich returned to his original assumption that the granules are secretory products of the cells, and defined his standpoint at that time as follows:
"Did the neutrophil granulations really represent the bodies which supply these cells with oxygen, as Altmann supposes, a condition such as we have here brought [Pg 130] forward would be impossible, since with the disappearance of the granules death of the cells must follow. But from the point of view of the secretion theory the condition described is easily explainable. ”

“ Very constant also is a marked absolute, and often a relative, increase of eosinophiles and basophiles. Polymorphonuclear neutrophiles and lymphocytes are relatively decreased.
[p. 210] The red cells show the changes characteristic of a severe secondary anemia, except that nucleated reds are commonly abundant; in fact, no other disease gives so many. They are chiefly of the normoblastic type. Megaloblasts are uncommon. Blood-plaques are generally increased.
2. Lymphatic Leukemia.—This form may be either acute or chronic. There is marked loss of hemoglobin and red corpuscles. ”

“ The triacid stain is very convenient. It is much to be recommended for good general preparations; it is indispensable in all cases where the study of the neutrophil granulations is concerned.
3. Basic double staining. Saturated, watery methyl-green solution is mixed with alcoholic fuchsin.
The stain, which only requires a small fixation, is completed in a few minutes, and colours the nuclei green, the red blood corpuscles red, the protoplasm of the leucocytes fuchsin colour. It is therefore specially suited for demonstration preparations of lymphatic leukæmia. ”

“ The average amounted to 0.58%, a number, therefore, which is often to be found in healthy individuals. A leucocytosis of mast cells, comparable with the eosinophil or neutrophil forms of leucocytosis, has not been demonstrated in the cases of Canon or other observers. On the other hand, the mast cells undergo a considerable increase in myelogenic leukæmia, in many cases equalling or even exceeding that of the eosinophils. We shall not err in deriving the mast cells of the blood solely from the bone-marrow, on the grounds of this fact ”

“ These granules are identical with the corresponding granules in the leukocytes just described. The occurrence of two kinds of granules in the same cell is rare.
Myelocytes are the bone-marrow cells from which the corresponding granular leukocytes are developed. Their presence in the blood in considerable numbers is diagnostic of myelogenous leukemia. The neutrophilic form is the less significant. A few of these may be present in very marked leukocytosis or any severe blood condition, as pernicious anemia. ”

“ For instance, cigarette smoke, neutrophil elastase, and P. aeruginosa proteases are well-known inflammatory stimuli that can cause significant inflammatory responses, which result in goblet cell metaplasia and hyperplasia, leading in turn to mucin overproduction and mucus hypersecretion in airways [22] [23] [24] . Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) , interleukin (IL) -1β, IL-6, IL-8, IL-13, and IL-17 can upregulate the expression of MUC5AC, the marker of goblet cell metaplasia, through different signaling pathways [25] [26] [27] [28] [29] . ”

“ They have a single large nucleus which stains feebly and their bodies may show neutrophile granules. Larger and smaller nucleated red blood cells may be found in spleno-myelogenous leukæmia. The leucocytes are frequently in a condition of fatty degeneration, and there may be a decrease in the number of red blood cells. ”

“ In the red cells we have the picture of a rapidly developing pernicious anaemia The color index is above 1.
The leucocytes number about 20,000 of which 60 to 70% are neutrophiles. Immature neutrophiles, as the metamyelocyte, are very common.
Prophylaxis and Treatment
The transmitting agent not being known we are in the dark as to prevention. Evidence points to some arthropod biting at night as the incidence of the disease decreased when those working in the Oroya fever zone were compelled to leave the valleys before sundown. ”

“ An increase is very much more frequent, and is known as leucocytosis, though in this term is usually connoted a relative increase in the proportion of the polymorphonuclear neutrophile leucocytes. Leucocytosis occurs under a great variety of conditions, normally to a slight extent during digestion, during pregnancy, and after violent exercise, and abnormally after haemorrhage, in the course of inflammations and many infective diseases, in malignant disease, in such toxic states as uraemia, and after the ingestion of nuclein and other substances. ”

“ It is probably the best for neutrophilic granules. It is difficult to make, and should be purchased ready prepared from a reliable dealer. Nuclei are stained blue or greenish-blue; erythrocytes, orange; neutrophilic granules, violet; and eosinophilic granules, copper red. [p. 173] Basophilic granules and blood-plaques are not stained (see Fig. 85) .
Success in staining depends largely upon proper fixation. The film must be carefully fixed by heat: underheating causes the erythrocytes to stain red ”

“ On reaching the vicinity they leave the blood stream and join in the warfare—many performing their function of phagocytosis (q.v.) , others falling victims to the toxins. The tissues of the part become disorganized or destroyed, and their place is taken by the mass of warring cellular elements now recognized as pus.
As soon as the fluids and the polymorpho-nuclear leukocytes have succeeded in diminishing the virulence of the micro-organism, the second line of defenders—the large mononuclear leukocytes (fig. 23, Pl. II.) make their appearance at the field of battle in ever increasing numbers. ”

“ By eosinophilia we understand an increase only of the polynuclear eosinophil cells in the blood. Confusion of this form of leucocytosis with leukæmia is quite impossible, because a good number of characteristic signs are necessary for the diagnosis of the latter, as we shall have to explain in the next section. The presence of mononuclear eosinophil cells in the blood should not be regarded, as is the case in many quarters, as an absolute proof of leukæmia, for they are also found in isolated cases of ordinary leucocytosis. ”

“ But in certain directions, notably in regard to the relations with micro-organisms, changes in the blood-plasma can be made out, though they are not associated in all cases with changes in the formed elements which float in it, nor with any obvious microscopical or chemical alterations.
The phenomena of immunity to the attacks of bacteria or their toxins, of agglutinative action, of opsonic action, of the precipitin tests, and of haemolysis, are all largely dependent on the inherent or acquired characters of the blood serum. It is a commonplace thatImmunity. ”