THE DYNAMICS OF LEUKOPENIA AND LEUKOCYTOSIS†

Abstract

Certain aspects of the physiology of granulocyte and lymphocyte production and circulation have been presented. In normal human granulocyte physiology the maturing cell spends a period of about 5 days in the "marrow granulocyte reserve" (MGR). The cells in the MGR are products of the proliferating myeloid tissue, and the relative sizes of these marrow "compartments" have been calculated by others. The MGR contains a volume of maturing cells some 20 to 25 times the number estimated in the circulating blood. DNA-labeling experiments, combined with leukopheresis and other methods of inducing leukopenia and leukocytosis, have shown that granulocytes circulate freely for variable but brief periods, and may be sequestered in various capillary beds for most of their intravascular life. The average time spent in the circulation appears to be between 4 and 8 hr. Once the granulocytes leave the vascular system entirely and migrate into tissue spaces, they do not appear to reenter the circulation in significant numbers. The MGR is the most important factor in the development of an acute leukocytosis as induced by leukopheresis, in-travenous bacterial endotoxin and experimental peritonitis. The adequacy of the MGR can usually be assessed by correlation of blood and marrow morphology with the granulocytic response to a purified bacterial lipopolysaccharide, Pyrexal. The response to Pyrexal has been studied in a variety of clinical states, and has been found to be of use in patients undergoing therapy with myelotoxic agents. A normal response is strong evidence for adequate marrow granulocytic reserves. However, the failure to develop a leukocytosis in the normal range must be interpreted in the light of other clinical findings, since it may be due to accelerated removal of cells peripherally, rather than to depletion of the MGR. The physiology of lymphocytes is as yet poorly understood. Present evidence suggests that lymphocytopoiesis may take place in a variety of tissues as well as in lymph nodes, lymph and blood. It is pointed out that the isotopic data previously interpreted as showing a very long survival time for the mature lymphocyte may actually reflect the very slow turnover by growth of the large mass of lymphocytopoietic tissue.