Production of Monocytes and Epithelioid Cells in Subcutaneous Tissues by Injection of Various Irritants. ∗

In the course of a study upon hepatic injury and the possible relationship of such injury to the white blood cells, Lawrence and Huffman 1 , 2 , 3 found that the subcutaneous injection of guinea pigs with yellow phosphorus (in oil) was followed by an elevation of the monocytes in the circulating blood. These findings suggested that the study of the subcutaneous tissues of animals injected with the same material might aid in determining the cause and site of the production of the monocytes.

It has been repeatedly demonstrated that the injection of many supposedly inert substances (e. g., waxes, oils and various colloidal bodies) is followed by local reactions which are similar to those seen in fixed sections of tuberculous tissues. With the methods involving fixation and sectioning, it has been possible to locate groups of epithelioid cells in the tissues; but these methods have not given us any very satisfactory help in identifying epithelioid cells when occurring singly or scattered in the tissues. The use of the supravital method of staining 4 , 5 has added certain criteria to those already known and has made possible the recognition of the epithelioid type of cell (including the epithelioid cell of tuberculosis) even when seen entirely alone in the connective tissues. The principal factor in this characteristic appearance is the presence of many fine droplets in the cytoplasm (granules or vacuoles) which stain with neutral red, and the later appearance of refractive droplets in the periphery of the cell. 6 The development of these characteristic cells (epithelioid) in tuberculous areas was demonstrated by Cunningham, Sabin, Sugiyama and Kindwall, but these observers did not pursue their studies into an analysis of the nature of the basic stimulus of this production or modification, or into the possible production of monocytes and epithelioid cells under other abnormal conditions.

The present studies have been made with the supra-vital technique referred to above, both neutral red and Janus green being used. Guinea pigs have been used throughout and all animals have been carefully autopsied at the end of the experiment to rule out inter-current infection. Phosphorus dissolved in almond oil, olive oil, or a mixture of both; almond and olive oils alone; and mineral oil have been used for the subcutaneous injections. Very small amounts were given in the subcutaneous tissues of the anterior abdominal wall, the area was carefully marked and the animal kept for various intervals before final study. At the time of study, the animal was killed with chloroform and the area of the injection exposed.