TY - JOUR
T1 - A kinetic model of bone marrow neutrophil production that characterizes late phenotypic maturation
AU - Orr, Yishay
AU - Wilson, David P.
AU - Taylor, Jude M.
AU - Bannon, Paul G.
AU - Geczy, Carolyn
AU - Davenport, Miles P.
AU - Kritharides, Leonard
PY - 2007/4/1
Y1 - 2007/4/1
N2 - Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic 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-/CD16 low 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 × 109·l-1·min-1), warming (0.14 ± 0.02 × 109·l-1·min -1), and weaning (0.12 ± 0.06 × 109· l-1 ·min-1) 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 h 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 postmitotic neutrophils that are CD10+ increases from 64 to 81% during these sampled 8.4 h of maturation.
AB - Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic 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-/CD16 low 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 × 109·l-1·min-1), warming (0.14 ± 0.02 × 109·l-1·min -1), and weaning (0.12 ± 0.06 × 109· l-1 ·min-1) 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 h 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 postmitotic neutrophils that are CD10+ increases from 64 to 81% during these sampled 8.4 h of maturation.
KW - Bone marrow
KW - Granulopoiesis
KW - Mathematical modeling
KW - Neutrophil recruitment
KW - Postmitotic maturation
UR - http://www.scopus.com/inward/record.url?scp=34147108642&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00627.2006
DO - 10.1152/ajpregu.00627.2006
M3 - Article
C2 - 17185405
AN - SCOPUS:34147108642
SN - 0363-6119
VL - 292
SP - R1707-R1716
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -