THE FATE OF THE GIANT CELLS WHICH FORM 
IN THE ABSORPTION OF COAGULATED * 
BLOOD SERUM IN THE ANTERIOR 
CHAMBER OF THE RABBIT’S 
EYE 
BY 
LUDVIG HEKTOEN 
From 
THE JOURNAL (*F EXPERIMENTAL MEDICINE 
Vol. 111, No. 6, 1898 THE FATE OF THE GIANT CELLS WHICH FORM IN THE 
ABSORPTION OE COAGULATED BLOOD SERUM IN 
THE ANTERIOR CHAMBER OE THE RABBIT’S EYE. 
LUDVIG HEKTOEN. 
Plate LI. 
In this article it is the purpose to describe briefly the results of 
some experiments which show that the multinucleated giant cells 
which form during the absorption of foreign bodies in the tissues may 
divide into viable cells. 
Concerning the extensive literature about giant cells—their forma- 
tion, function and fate—reference is made to the article in this 
Journal by the writer entitled “ The Fate of Giant Cells in Healing 
Tuberculous Tissue as observed in a Case of Healing Tuberculous 
Meningitis,”* in which it is pointed out that giant cells in tuber- 
culous tissue, under certain conditions, undergo progressive changes 
and separate into small living cells. 
Small pieces of sterile, solidified blood serum, such as is ordinarily 
used as a culture medium, were inserted under aseptic precautions 
and cocaine anaesthesia into the anterior chambers of several healthy 
rabbits’ eyes through a small incision in the sclera near the corneal 
margin. Once a bit of sterile potato wras introduced. These opera- 
tions were skilfully made for me by Dr. Cassius D. Westcott, In- 
structor in Ophthalmology in Rush Medical College, and I wish to 
thank him for his kind aid. 
THE EXPERIMENTS. 
After perfecting the technique the operations were followed by 
but little reaction; in some instances the vessels in the sclera were 
congested for three or four days, the cornea rather cloudy, the anterior 
* The Journal of Experimental Medicine, iii (1898), 21. 574 
The Fate of Giant Cells 
chamber turbid, and more or less photophobia was apparent. Soon 
after their implantation a small greyish white rim would become 
visible around the foreign bodies, which gradually disappeared until, 
if allowed, only a small, greyish, semi-opaque thickening in the inner 
surface of the cornea remained. In a few cases the blood serum was 
gradually dissolved without any accumulation taking place around it, 
the cornea and anterior chamber remaining perfectly clear. In the 
case of the bit of potatol and when pieces of dry and hard serum were 
used, the absorption always proceeded slowly and with well-marked 
anatomical changes. 
The animals were killed at intervals of from a few days to six 
or more weeks after the operation. The eyes were fixed in corrosive 
sublimate and the piece of cornea and iris, including the site of the 
foreign body, embedded in paraffin, cut serially, fixed on the slide 
and stained with hematoxylin and eosin, van Gieson’s stain, etc. 
Comparatively slight attention was given the study of the early 
changes. Suffice it to say that the emigration of leucocytes from the 
vessels of the iris took place to a limited extent only, at least in 
the cases in which bits of solid blood serum are concerned. The 
leucocytes present were of the polymorphonuclear variety, and they 
appeared to become loaded early with granules of serum, after which 
some of them returned to the iris, in which a few collections of such 
cells were found. In the later stages of the resorptive process leuco- 
cytes were not observed. 
THE HISTOLOGICAL EXAMINATION. 
The new cells produced come almost wholly, it would seem, from 
the layer of polyhedral cells clothing the inner surface of the posterior 
elastic lamina (Descemet’s membrane) and the anterior surface of the 
iris. The posterior lamina itself generally remains quite intact. The 
new cells, which are round, oval or polyhedral, accumulate around the 
foreign body and penetrate into its interior, generally breaking it up, 
so that there is formed a mass of cells which adheres to the elastic 
layer and encloses the granular detritus of the coagulated serum. 
Most of the cells take up granules into the interior of their cytoplasm, 
often to such an extent that the nucleus and the entire cell appear as Ludvig Hektoen 
575 
if buried beneath the granular mass. The serum granules, whether 
free or intracellular, are easily recognizable because of their brownish 
or golden yellow color (derivatives of haemoglobin pigment). 
During this time there are formed a small number of multinu- 
cleated giant cells or plasmodial masses, which appear, as far as these 
observations show, to result from fusion of many small cells. These 
giant cells do not differ in form and in their general characteristics 
from those ordinarily observed in connection with the absorption of 
sterile foreign bodies elsewhere. Their size and the number of nuclei, 
which are scattered uniformly throughout the body of the cell, vary 
considerably. In the earlier stages the cells are loaded with serum 
granules and are of circular outline (Plate LI, Pig. 1); later when 
the foreign body has been largely removed the giant cells become 
oval or oblong, due, it would seem, to the pressure of the new fibres 
that in the meantime have formed around them (Plate LI, Fig. 3). 
The granules of solid blood serum without and within the cells 
gradually disappear, largely, it would seem, by means of a process of 
intracellular digestion or solution; in some of the giant cells as well 
as in the smaller cells occur vacuoles in the cytoplasm containing 
granules; some of the serum, but not much, is also transported into 
the iris by leucocytes. 
Simultaneously with the destruction or removal of the foreign 
granules the uninuclear and multinuclear cells begin to show further 
and progressive changes that ultimately lead to the formation of a 
layer of tissue which much resembles the cornea in structure. These 
changes begin first and are farthest advanced at the periphery of the 
cell mass, extending little by little throughout the central parts. 
The changes consist in the production of a fibrillated intercellular 
substance, or stroma, while at the same time the cells become spindle- 
shaped and elongated, the nuclei more slender and fusiform. All the 
stages in this transformation of embryonal cells to mature tissue, 
during which the granules of serum are destroyed, can be quite readily 
traced. In the later stages the fibrillse of the new stroma are gathered 
together into interlacing bundles of considerable thickness (Plate 
LI, Figs. 2 and 3), the general course of which is parallel with 576 
The Fate of Giant Cells 
that of the corneal lamellae, from which they are separated by the 
intact posterior elastic lamina. While the course and arrangement of 
these new fibres are identical with those of the cornea, yet the new 
lamellae are not so thick and densely interwoven as those in the cornea 
and they stain more deeply with eosin. This new tissue, the free 
surface of which becomes covered by a distinct endothelial lining, 
may finally appear as a mere rounded or pyramidal-shaped thickening 
on the posterior surface of Descemet’s membrane (Plate LI, Pig. 4), 
or it may unite the cornea with the iris, especially if the foreign body 
found a resting place in the irido-corneal angle. 
Lying in the spaces of the new tissue, sometimes apparently upon 
its fibres, are small cells like connective tissue cells, occasionally cells 
containing granules as well as free heaps of serum detritus and, in 
the stages not too far advanced, multinucleated giant cells in the pro- 
cess of separation into uninuclear cells. 
It has already been stated that in the earlier stages the giant cells 
are more or less circular and the margins smooth and even. As the 
fibril! ated stroma forms about them they may in many cases become 
oval and even distinctly oblong (Plate LI, Pig. 3), simultaneously 
with the disappearance of the serum, the long diameter corresponding 
to the direction of the fibres of the stroma. At this time they are 
usually entirely, or almost entirely, free from granules of serum; 
occasionally there may be vacuoles containing granules in the proto- 
plasm. It should be emphasized that there are no signs of degenera- 
tion in the giant cells; the cytoplasm is reddish when stained by eosin 
and sometimes finely granular, but often it appears dense and homo- 
geneous; the nuclei stain perfectly, and in one instance a dividing 
nucleus in the daughter star stage was observed in a giant cell. 
As the serum disappears more or less distinct lines of cleavage be- 
come visible in the giant cells, at first most marked at the periphery; 
the margin is not smooth and even, but is fringed by the spindle- 
shaped projections of partly separated cells which seem to have a 
tendency to arrange themselves parallel with the fibres of the stroma 
(Plate LI, Pig. 3). Single uninuclear cells exactly similar to these 
partly detached masses are occasionally found about the giant Ludvig Hektoen 
577 
cells. In some giant cells, especially those encountered in the older 
and firmer parts, there are lines of separation throughout their entire 
extent (Plate LI, Fig. 3), running in such a manner that single 
nuclei surrounded by more or less cytoplasm are completely or in- 
completely mapped out; it is noteworthy that in these cells the lines 
of cleavage map out more or less distinctly spindle-shaped cells, the 
long axes of which correspond in direction to the fibres of the stroma. 
Occasionally the lines separating a nucleated mass are so broad and 
well marked that it appears as though a distinct cell wTere lying in a 
vacuole; the cytoplasm of such giant cells especially seems firm and 
condensed; the splitting up apparently takes place more slowly, and 
the impression is received that this may all be caused by the pressure 
exerted upon the giant cell by the fibrillated stroma in which it is 
enclosed, or that the cytoplasm is being transformed into the same 
sort of substance as the fibres of the stroma. The separation of small 
cells nevertheless continues, because in the older tissue are found 
small giant cells containing a few—three or four—nuclei and em- 
bedded in a dense capsule of nucleated fibrous tissue, without any 
traceable evidences of nuclear disintegration or of destruction of the 
giant cells by phagocytes. 
When the serum is absorbed rapidly and the giant cells lie in the 
broad and loose meshes of the new-formed fibrillated tissue, the lines 
of cleavage may be quite complete, so that single nuclei, surrounded 
by an irregularly shaped bit of cytoplasm, are split off and imperfect 
giant cells result, which are surrounded by uninuclear small cells that 
fit the depressions and elevations on the remnant of the subdividing 
plasmodial mass. Uninuclear cells thus produced present no signs 
of necrobiosis and can be traced by means of transition stages into 
the elongated and flattened cells above described as lying in the new- 
formed tissue. Uuclear and protoplasmic detritus, as well as evi- 
dences of immigration of small cells or leucocytes into giant cells, are 
not to be observed. 
CONCLUSION. 
The conclusion seems warranted that the giant cells formed in the 
absorption of coagulated blood serum inserted into the anterior cham- 578 
The Fate of Giant Cells 
ber of the rabbit’s eye subdivide again into uninuclear small cells that 
take part with other new-formed cells derived from the lining of this 
space to form a densely fibrillated mass of tissue that resembles quite 
closely the cornea in its structure. 
This demonstration materially strengthens the opinion expressed 
by the writer in his previous article in this Journal,* that the giant 
cells in healing non-degenerated tuberculous tissue may separate into 
small living cells, and that the giant cells of tuberculosis are not 
necrobiotic elements from the very moment and from the very mode 
of their formation, as has been the general teaching, especially in 
Germany. 
DESCKIPTION OF PLATE LI. 
Pig. 1.—Recent giant cell with rounded and smooth margin filled with 
granules of serum so that the nuclei are covered over. 
Pig. 2.—Photo-micrograph. Separating giant cell lying in the meshes of 
new fibrous tissue and surrounded by cells and by a cell mass which appear 
to have been sundered from the larger mass; distinct lines of cleavage are 
seen in the smaller as well as in the larger mass, so that small uninuclear 
cells may be said to be separating. 
Photo-micrograph, 500 diameters, of eosin and hsematoxylin specimen. 
Same magnification and staining as in Fig. 1. 
Fig. 3/—Oblong giant cell with a dense protoplasm in which run distinct 
lines that subdivide the multinucleated mass into more or less well-marked, 
small, uninuclear cells. In the centre is a part of a cell lying in a distinct 
vacuole. From a late stage. To the left of the giant cell and the surround- 
ing thick fibres runs the intact posterior elastic lamina, and to the right is 
the substance of the iris. 
Photo-micrograph with same magnification and staining as in Fig. 1. 
Fig. 4.—Fusiform thickening of posterior surface of cornea, due to the 
formation of a densely fibrillated mass of new tissue after complete absorp- 
tion of the blood serum. The posterior surface of the new-formed mass is 
clothed with a single layer of endothelial cells which is continuous with the 
lining of the posterior surface of Descemet’s membrane. Close inspection 
will show the intact posterior elastic lamina running between the new tissue 
and the cornea. 
Photo-micrograph, 100 diameters, of eosin and hsematoxylin specimen. 
* Loc. cit. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. 111. 
PLATE LI. 
FIG. 1. 
FIG. 2. 
FIG. 3. 
FIG. 4. 
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