Neutrophil mobilization and clearance in the bone marrow

Abstract

SummaryThe bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony-stimulating factor (G-CSF). Mature neutrophils are continually released into the circulation, with an estimated 10 11 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half-life in the blood of $6Á5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell-derived factor (SDF-1a)/chemokine (C-X-C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co-ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow.

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

“…To corroborate the specificity of our observations of increased neutrophil mobilization and more severe intestinal injury in C3aR −/− mice, we next inhibited CXCR4, another innate immune receptor that negatively regulates the mobilization of various leukocyte populations, including neutrophils (18). Indeed, administration of the CXCR4 antagonist AMD3100 before IR injury significantly increased the total number of leukocytes after reperfusion, including neutrophil and mononuclear cell populations.…”

“…Analogous to the role of C3aR in hematopoietic stem/progenitor cells (29), our results suggest that a major function of C3aR expression on neutrophils is in regulating bone marrow-derived neutrophil mobilization after acute tissue injury. Previously identified endogenous factors influencing neutrophil mobilization include G-CSF, SDF-1, KC, and C5a (18). We now add C3a to this biological repertoire as another, negative modulator of neutrophil mobilization, similar to SDF-1.…”

“…Based on previous studies identifying C3aR as a negative regulator of hematopoietic stem/progenitor cell egress and mobilization (29), we hypothesized that the enhanced neutrophil infiltration in C3aR −/− mice could have been driven by increased mobilization of neutrophils into the circulation after IR injury, particularly because a large proportion of the body's mature neutrophils reside in the bone marrow, from where they can be rapidly mobilized in response to infection or trauma (18,30). C3aR −/− mice indeed showed a striking increase in the number of circulating neutrophils over WT mice after injury, but neither monocyte nor lymphocyte levels were increased with IR.…”

“…Finally, we assessed whether C3aR deficiency can also enhance neutrophil mobilization in the absence of tissue injury, by injecting WT and C3aR −/− mice with human recombinant G-CSF, a potent bone marrow neutrophil mobilizer (18). C3aR −/− mice mobilized significantly greater numbers of neutrophils compared with WT mice (Fig.…”

Peritoneal Dialysis Catheter Increases Leukocyte Recruitment in the Mouse Parietal Peritoneum Microcirculation and Causes Fibrosis

“…Inflammation involves neutrophil mobilization from the bone marrow into the blood (22). The total blood leukocyte counts were elevated in the catheterized groups but a significant increase was only observed in the catheter control group compared with naïve mice.…”