PHAGOCYTOSIS (Gr. φαγεῖν, to eat, devour, and κύτος, cell). Many cells of the body possess the property of engulfing particles, a character to be associated with their power of performing amoeboid movement. This property is termed phagocytosis. Primarily this phagocytic power was simply the means by which the cell took within its cell body food particles which were ultimately digested and assimilated. In the higher organisms, however, this property has been developed for different purposes, and in pathology at the present day a meaning wider than that above given is often included in the term. The particle having been taken into the cell, one of three things may happen. (1) The particle may consist of digestible material, in which case the cell secretes a digestive fluid, a food vacuole is formed, the particle is gradually dissolved by the secretion and the products absorbed into the cell substance. (2) The particle may be indigestible, in which case it is retained within the cell body for a time and ultimately discharged. The particle englobed may comprise almost any material, but if it is to serve as a food it must be of animal or vegetable origin. At the time of ingestion it may be dead or living. In the case in which it is living the organism is first killed and then digested, or (3) the organism may prove resistant, in which case it may multiply and finally destroy the cell, when a number of organisms are set free. This is one of the means by which, in the higher organisms, a local infection may become distributed through the organism. The digestion effected within a cell is fermentative in character Thus a proteolytic ferment has been prepared from the bodies of amoebae—the ferment possessing fairly active properties both in acid, neutral or alkaline media, but especially in the latter.
In studying the process of phagocytosis generally much information may be gained as to its general characters by the study of the processes of intracellular digestion in the simpler Invertebrates, a study largely extended by Metchnikoff and his co-workers in the elaboration of Metchnikoff's view of the nature of immunity. Thus, to take an instance from the sponges. Food substances, in the form of minute organisms, which have penetrated the pores of the sponge are seized by the ciliated or amoeboid cells lining those spaces, and are then killed and digested. In this case also the process of digestion is proved to be fermentative. It is readily understandable that we should find such cells on the external surface of an organism or on the surface lining the alimentary tract, particularly in the latter position. But in addition there are many cells within the body in which phagocytic power is retained and markedly developed. Such cells may be fixed or wandering cells. They are employed for removing foreign material or debris which may occur within a tissue. For instance, as the result of an injury, inflammatory process, &c., cells and other structures of a tissue may be destroyed. One of the processes of repair consists in the removal of the resulting debris, which is effected by phagocytes. A similar process is seen with red blood corpuscles which may have escaped into a tissue through rupture of capillaries. Foreign particles accidentally gaining admission to a tissue are in many cases removed in a similar manner, e.g. soot particles which have passed through the respiratory surface are then largely removed by phagocytes and carried to the bronchial lymphatic glands. Very commonly living organisms effect an entrance through wound surfaces, the alimentary surface, &c., and one of the processes employed for their destruction and removal is that of phagocytosis.
As an illustration of the removal of foreign red blood corpuscles we may take the experiments of Metchnikoff in which a small drop of defibrinated blood of the goose was injected under the skin of a snail. The corpuscles quickly spread through the haemolymph of the snail, which by itself, however, effects no change in them. At the end of several hours examination shows that the leukocytes of the snail have englobed a large number of the red corpuscles. The following day intact corpuscles can still be found in the haemolymph, but the major number have already been devoured by the leukocytes. When taken up by a phagocyte the red corpuscle becomes round and its wall permeable. A vacuole is formed around the corpuscle, in which dissolved haemoglobin can be seen; a part of this haemoglobin also passes into the nucleus of the red corpuscle, proving that it too has been profoundly altered. Many of the nuclei are discharged. After some time the only parts of the corpuscle remaining are pieces of the nucleus and the peripheral layer of the corpuscle. Frequently the phagocytes, after having devoured one or several red corpuscles, themselves become a prey to their fellows. Analogous changes are observed in the tissues of a mammal when blood which has been extravasated is being removed, e.g. after a bruise. The first effect of the haemorrhage is an exudative inflammation, during which leukocytes arrive in large numbers and engulf the corpuscles. In the process of digestion which follows the haemoglobin is altered and new pigments formed from it. In mammals this pigment is dark red or brownish, in the pigeon it is green. Finally the corpuscles are completely digested. Analogous phenomena may be observed in connexion with the removal of cell debris resulting from any injury. Numbers of phagocytes may be found at work in this direction, for instance in the pus formed within an aseptic abscess. Hence we may regard the phagocytes as acting as the scavengers of the tissues
In the instances we have been dealing with the phagocytes are chiefly of the class of wandering cells and are brought to the seat of their activity by the blood. In examining any tissue where the process is going on it is seen that the phagocytes have accumulated there in large numbers. They have been attracted to the damaged area. The mechanism which effects this attraction is a chemical one—chemiotaxis. At the seat of the change chemical substances are produced which act upon the phagocytes, causing them to migrate towards the source—positive chemiotaxis. Apparently the material dissolving from cell débris can act in this manner. Thus if a capillary tube filled with a tissue extract be inserted under the skin of an animal, within a short time it will be found to be surrounded with numbers of leucocytes, which may also have encroached into the tube itself. As in other instances of chemiotaxis the same chemical stimulus in a higher concentration may repel the cells—negative chemiotaxis. Instances of this are especially frequent in relation to micro organisms and phagocytes, to which we may now turn.
That phagocytes can paralyse, kill and digest many microorganisms is the main fact in Metchnikoff's theory of the nature of immunity. The reaction may be readily studied by injecting a small quantity of a fluid culture of some mildly pathogenic organism into the peritoneal cavity of an animal, and in the course of an hour or so examining a smear from the surface of the omentum, when an abundance of phagocytes enclosing the organism 1n different stages of digestion will be found. Or we may adopt Leishman's method, in which a few drops of human blood are diluted with saline solution and centrifuged. The layer of white corpuscles is pipetted off, suspended in serum, and a minute drop of a suspension of a pathogenic organism is added. The preparation is then incubated at 37° C. for a quarter of an hour. Upon examining a drop of this mixture a number of bacteria are found within the phagocytes. Thus this attack and destruction of bacteria by phagocytes may take place within the body or by cells removed from the body. Whether or no a phagocyte can engulf bacteria is dependent upon a number of factors—partly specific properties of the phagocyte, partly factors varying with the constitution of the body serum. Thus Wright and Douglas, employing Leishman's method, have proved that leucocytes do not take up bacteria freely unless the serum in which they are suspended contain opsonins. They found, for example, that leucocytes taken from a patient suffering from a pyococci infection if suspended in normal human serum take up the cocci abundantly, whereas if the same leucocytes are suspended under similar conditions in the patient's own serum the reaction may be almost absent. Further, leucocytes taken from a normal individual and suspended in the patient's serum are practically inactive, while the same phagocytes in normal serum are very active. Exactly how the substance in the serum acts is undecided, but it has been proved that there are in serum substances which become fixed to bacteria and which render them an easier prey to the phagocytes. This specific opsonin is used up when the bacteria are added to the serum, so that if the bacteria are subsequently removed the serum is no longer active. There is evidence too that there is a multiplicity of opsonins. As to the origin of the opsonins ue have no certain evidence. It is suggested that they are a secretion from the leucocytes themselves and that it is an evidence of another and preliminary mode of attack possessed by the leucocyte, viz the discharge of a secretion from the cell which is to damage or paralyse the bacterium and thus enable the phagocyte to engulf it.
The mechanism of destruction of a bacterium once it has been taken up by a phagocyte is probably, just as in the instance of dead cellular material, one of intracellular digestion. The bacterium before being engulfed is probably inert in most instances, though it may yet prove too strong for the phagocyte. The next stage we can trace is the formation of a vacuole around the organism, or, if the latter be large, around a part of the organism, and the part thus surrounded quickly shows signs of destruction. For instance, its staining reactions become weaker. When a part only of the organism is surrounded by a vacuole the part thus surrounded soon ceases to stain, while the remaining part stains normally, and we thus have a marked contrast evidencing the two stages.
In the next place we must ask which are the cells possessing phagocytic powers? Leaving apart the cells lining the alimentary tract (because we know practically nothing of their power in this respect) a number of free cells possess amoeboid properties as well as also a number of fixed cells. These latter are attached to certain spots of a tissue, but are capable of throwing out processes which can seize upon particles of foreign matter or even upon certain elements of the same organism. Of this category Metchnikoff distinguishes the nerve cells, the large cells of the spleen pulp and of lymph glands, certain endothelial cells, the neuroglia cells, and perhaps certain cells of connective tissues. All these elements can under certain conditions act as phagocytes, and with the exception of the nerve cells all are of mesoblastic origin. Those of greater importance on account of their greater activity in this respect are the large splenic and lymph cells, the neuroglia cells and certain endothelial cells. With regard to the wandering cells Metchnikoff considers that some are certainly non-phagocytic, for instance the lymphocytes. According to Metchnikoff it is only when these cells become older and have developed a nucleus rich in chromatin and an abundant cell body that these cells develop phagocytic properties. This is the large hyaline leucocyte. The polymorphonuclear and the eosinophil leucocyte are both phagocytes. Metchnikoff therefore divides the phagocytes into two classes—the microphages, comprising the polymorphonuclear and the eosinophil cell, and the macrophages, containing the large hyaline cell, the cell of the splenic pulp, the endothelial cell and the neuroglia cell. From further observation of these cells he concludes that the microphages are chiefly concerned in opposing the micro-organisms of acute infections, whereas the macrophages are chiefly concerned in combating chronic infections. It is the macrophage also which is concerned in removing cell débris, e.g. red corpuscles from a hemorrhage or the red corpuscles of another animal which may have been introduced experimentally.
Metchnikoff and his co-workers have shown that the two principal groups of leucocytes are generally spread throughout the vertebrates. Thus instances of each kind are found even in the lamprey, though here their staining properties are feebler; also cells which show but small differences from the analogous cells of mammals are found in the alligator. (T. G. Br.)