Amongst the granule-free forms the giant cells deserve special mention, for they are an almost constant constituent of the bone-marrow of the mammalian class. According to the recent researches of Pugliese the giant cells are considerably increased after extirpation of the spleen in the hedgehog; an organ of quite extraordinary size in this animal and doubtless therefore possessing important hæmatopoietic functions.
Pugliese asserts that in the hedgehog after splenectomy the nucleated giant cells pass into leucocytes by amitotic nuclear division. Unfortunately in his preliminary communication there are no notes of the granules of the bone-marrow cells.
On examining a stained dry preparation of the bone-marrow of the guinea-pig, rabbit, man, etc. it is seen that the characteristic finely granular cells are present in all stages of development, from the mononuclear through the transitional to the polynuclear (polymorphously nucleated) forms, which we meet with in the circulating blood. A glance at a preparation of this kind shews that the bone-marrow is clearly the factory where typical polynuclear cells are continuously formed from the granule-containing mononuclears.
Here also the same process of ripening can be seen in the polynuclear eosinophil leucocytes.
Ehrlich has been able by special differential staining to bring forward proof that the constitution of the granulation changes during the metamorphosis of the mononuclear to the polynuclear cells. In the young granules there is prominent a basophil portion that becomes less and less marked as the cell grows older. 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.
It is still impossible to judge with certainty the rate at which the ripening of the mononuclear to the polynuclear cells proceeds, or further to decide if the ripening of the granules always runs parallel in point of time with that of the whole cell. On the grounds of our observations we would suppose that in general the two processes run their course side by side, but that in special cases the morphological ripening of the cell may proceed more rapidly than that of the granules. It is particularly easy to observe this point in eosinophil cells. Ehrlich had already mentioned in his first paper (1878) that side by side with the typical eosinophil granules isolated granules are often found which shew a deviation in tinctorial properties: for instance, they stain more of a black colour in eosine-aurantia-nigrosin; in eosine-methylene-blue, bluish-red to pure blue. Ehrlich had already described these as young elements in his first paper. The same differences are found more sharply marked in leukæmia even in the circulating blood, in the neutrophil as well as in the eosinophil group. Ehrlich has repeatedly found in leukæmic blood polynuclear eosinophil cells, whose granules must almost exclusively be regarded as young forms[15].
Ehrlich regarded these as typical examples of a relative acceleration of the morphological ripening of the cells, as compared with the development of the granules.
In normal blood we find only the ripe forms of the specific granulated cells of the bone-marrow. The mononuclear and transitional forms of the neutrophil group, do not under normal circumstances pass over into the blood-stream.
Ehrlich regarded the mononuclear neutrophil granulated cells as characteristic for the bone-marrow, since they are found exclusively in the bone-marrow, never in the spleen or lymph glands, and for this reason named them "myelocytes," κατ' εξοχην[16]. When myelocytes, no matter of what size, appear in considerable numbers in the blood of an adult, a leukæmia of myelogenic nature is nearly always present. (For the very rare exceptions to this rule, which it may be added can never be confused with leukæmia, see pages 77, 78.)
Exactly similar conditions hold good for the eosinophil cells, in as much as the singly nucleated forms, which one may call eosinophil myelocytes, occur, almost exclusively, in leukæmic blood. These forms, which were first recognised by H. F. Müller, are however of less importance, for in myelogenic leukæmia the chief part of the foreign admixture of the blood is made up of Ehrlich's myelocytes.