Submitted on September 2, 2006
Accepted on December 18, 2006
A kinetic model of bone marrow neutrophil production which characterizes late phenotypic maturation
Yishay Orr1, David P Wilson2, Jude M Taylor2, Paul G Bannon3, Carolyn Geczy4, Miles P. Davenport2, and Leonard Kritharides5*
1 Centre for Vascular Research, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia; The Baird Institute for Applied Heart and Lung Surgical Research, Sydney, New South Wales, Australia
2 Centre for Vascular Research, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia
3 Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; The Baird Institute for Applied Heart and Lung Surgical Research, Sydney, New South Wales, Australia
4 Inflammatory Diseases Research Unit, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia
5 Centre for Vascular Research, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia; Clinical Research Group, The Heart Research Institute, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: l.kritharides{at}unsw.edu.au.
Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening post-mitotic maturation time and releasing younger neutrophils, however the kinetics of this change in maturation time remains unknown. We propose a kinetic model that examines the rate of change in neutrophil average age at exit from the bone marrow during active mobilization to quantify this response and use this model to examine the temporal profile of late neutrophil phenotypic maturation.
Total and CD10-/CD16low circulating neutrophils were quantified in cardiac surgery patients during extracorporeal circulation (ECC). Net growth in the circulating neutrophil pool occurred during the procedural (0.04 ± 0.02 x109/L/min), warming (0.14 ± 0.02 x109/L/min) and weaning (0.12 ± 0.06 x109/L/min) phases of ECC. When applied to our differential equation mathematical model, these results predict that neutrophil average age at exit from the bone marrow decreased continually during ECC, resulting in average neutrophil release 8.44 ± 2.20 hours earlier during the weaning phase than at the beginning of ECC sampling. Modeling of concurrent changes in CD10-/CD16low neutrophil numbers indicates that CD10 expression is directly related to neutrophil mean age and predicts that the proportion of mobilizable post-mitotic neutrophils which are CD10+ increases from 64% to 81% during these sampled 8.4 hours of maturation.
