A STUDY OF THE MECHANISM OF NUCLEINATE-INDUCED LEUCOPENIC AND LEUCOCYTIC STATES, WITH SPECIAL REFERENCE TO THE RELATIVE ROLES OF LIVER, SPLEEN, AND BONE MARROW.

The leucopenia induced by sodium nucleinate has been followed by repeated counts made simultaneously from the blood of a peripheral vein and from the internal organs, combined with a study of histological sections of the same organs taken with the counts. Measurements with the oncometer of changes in volume of the spleen have been correlated with the leucopenia and the leucocytosis following sodium nucleinate. It has thus been determined that the leucopenia is not the result of a vasomotor phenomenon, or of a change in blood volume, nor is it secondary to a retention of the white cells in the capillaries of lung or liver; it is due to the accumulation of neutrophilic leucocytes in the parenchyma of the spleen. That the spleen is solely responsible for the temporary depression of white cells in the general circulation under these conditions has been shown by splenectomy. In splenectomized rabbits no leucopenia developed, but instead a leucocytosis due to a direct action on the bone marrow. A profound change occurs in the distribution of the cells in the circulation at the moment of death. The liver, within a minute of the cessation of the circulation, shows a three- to fourfold increase in the number of white cells per c.mm., the differential count remaining unchanged. Thus estimations of the physiological distribution and redistribution of cells in the living state may be made only with the circulation unimpaired. The injection into normal rabbits of adenine and guanine nucleotides, split products of nucleic acid, gave immediate leucocytosis of bone marrow origin similar to that observed with the more complex molecule when the spleen was eliminated. The response of the bone marrow to chemotactic stimuli, such as those have used, may be reflected in the general circulation, through an absolute increase of young neutrophilic leucocytes, within a period of less than 1 hour. Within this brief period there takes place maturation from Myelocyte C and metamyelocyte into the early motile leucocyte, and the delivery of these just matured cells into the circulation. The response to one injection of nucleinate or nucleotide may persist into the 3rd and 4th days with a gradual depletion of the normal reserve of Myelocytes C in the bone marrow.