Simulation of murine granulopoiesis.

A mathematical model of granulocyte formation and its regulation has been made, using three negative feedback loops (i.e., two "chalone loops" and one "leucocytosis-inducing factor loop", as well as a short-lasting signal to cell division, induced by cell death. Experimental regeneration curves obtained after treating mice with two injections of cyclophosphamide or with one injection of vinblastine were reasonably well simulated. The simulations suggested that (i) immature granulocytes have a considerable capacity for additional mitoses (self-renewal); (ii) if an inhibitor of cell multiplication (chalone) is an important regulatory factor, it may be produced not only by mature, but also by immature granulocytes; and (iii) chalone may affect maturation times as well as generation times. It is possible to test experimentally these and other deductions mode from the model.