quantitative analysis of mechanisms that govern red blood cell age structure and dynamics during anaemia定量分析的管理机制在贫血红细胞年龄结构和动力学.pdfVIP

Quantitative Analysis of Mechanisms That Govern Red Blood Cell Age Structure and Dynamics during Anaemia 1 1,2 1,2 Nicholas J. Savill *, William Chadwick , Sarah E. Reece 1 Centre for Infectious Diseases, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom, 2 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom Abstract Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs). Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes) in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ) and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In th