A kinetic model of bone marrow neutrophil production that characterizes late phenotypic maturation

Abstract

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−/CD16lowcirculating 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−/CD16lowneutrophil 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.

A Distinct Subset of Proinflammatory Neutrophils Isolated from Patients with Systemic Lupus Erythematosus Induces Vascular Damage and Synthesizes Type I IFNs

“…Similarly, it is unclear what the significance is of the trend observed for decreased CD10 expression in LDGs, as assessed by mean fluorescent intensity by FACS, when compared to control or autologous lupus neutrophils. CD10 is a cell surface enzyme with neutral metalloendopeptidase activity that cleaves and inactivates multiple proinflammatory and vasoactive molecules(92) and whose expression is directly related to neutrophil mean age(93). There is evidence that neutrophil CD10 expression decreases significantly in response to in vivo inflammatory challenges (94).…”

“…Importantly, CD10 is only expressed by segmented neutrophils and not by earlier myeloid progenitors. While a CD10 − /CD16 low phenotype has been proposed to identify greater numbers of phenotypically immature neutrophils than does cellular morphology alone(93), the vast majority of LDGs expressed CD10, even if maybe at lower levels than the other neutrophils subsets. Nevertheless, this observation further suggests that potential abnormalities in neutrophil development may be involved in the generation of LDGs.…”

Circulating Immature Granulocytes With T-Cell Killing Functions Predict Sepsis Deterioration*

“…Decreased expression of CD10 and CD16 on granulocytes is characteristic of immature myeloid cells (8,(43)(44)(45). In contrast, both CD10 dim and/or CD16 dim granulocyte proportions predicted clinical deterioration of patients with sepsis and were associated with survival rates, as well as DR dim monocytes in a less extent.…”

“…An increased percentage of band cells (supposedly newly emerged neutrophils) has long been described within the first hours of sepsis onset (8). An increased percentage of band cells (supposedly newly emerged neutrophils) has long been described within the first hours of sepsis onset (8).…”

Role of neutrophils in innate immunity: a systems biology‐level approach

“…However, induction of neutrophilia during acute inflammation accelerates recruitment from bone marrow. Depletion of the stored basal reserves results in a decrease in post-mitotic maturation time to 3–4 days [22] and elicits additional release of functionally competent immature forms [23]. Granulopoiesis and PMN egress from bone marrow is enhanced by several immunomodulatory factors including GM-CSF, G-CSF, IL-8, and glucocorticoids [18, 24, 25].…”