Modification of granulocytopoietic cell proliferation by granulocyte extracts

Saline extracts of mature granulocytes have been partially purified by an ultrafiltration technique. The fraction in the 500-2000 daltons molecular weight range was retained and tested in a variety of experimental systems. Comparable fractions of erythrocyte and lymphocyte extracts were used for control purposes. Measurement of the structuredness of the cytoplasmic matrix (SCM) of cells is shown to be a very sensitive measure of the effects of the extract. Specific and reversible increases in SCM of proliferating granulocytic cell populations indicate changes compatible with reduced proliferation and these are confirmed by autoradiographic observations following tritiated thymidine labelling. Repeated labelling experiments to obtain the rate of flow of cells through the cycle gave a mean cell cycle time of 15 hrs in the controls but in animals treated with the granulocyte extract this was increased to about 30 hrs. The duration of DNA synthesis was increased slightly but there was no effect on G2 as measured by the stathmokinetic index method. Cell production in developing spleen colonies was reduced by repeated doses of the extract over a period of 4 days. Approximately two cell doublings were lost during this period due to the prolonged cell cycle.