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Granulocytopoiesis. I. Senescence and Random Loss of Neutrophilic Granulocytes in Human Beings

T. M. FLIEDNER, E. P. CRONKITE and J. S. ROBERTSON

Abstract

Tritiated thymidine labeling of DNA with a subsequent autoradiographic and cytologic study of the peripheral blood and oral lavages reveal:

1. Direct cytologic evidence for a random loss of granulocytes from the blood into the oral cavity is given. Presumably there are larger random losses in the gastrointestinal tract. This observation supports the conclusions based upon disappearance of radioactivity from the blood after autotransfusion of DFP32 labeled granulocytes.

2. The delayed appearance of label in the pyknotic granulocytes (Ab-bauformen) is strong evidence that those cells are older degenerating granulocytes and that it takes about 24-30 hours for labeled granulocytes to age to the point of becoming pyknotic senescent granulocytes.

3. The process of senescence truncates the exponential curves of random disappearance of granulocytes from the blood.

4. A model showing the relationship between random loss and senesence is constructed and discussed.

5. A mathematical description of this model is presented. The equations developed are highly sensitive to variations in input data thus limiting their practical usefulness for computations unless precise measurements are possible and are made on each subject studied for each variant in the equation.