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Inhibition in vivo of mouse granulopoiesis by cell-free activity derived from human polymorphonuclear neutrophils
Abstract:
Cell-free extracts from human polymorphonuclear neutrophils (PMN) inhibited rebound granulopoiesis in the bone marrow and spleen of mice pretreated with cyclophosphamide to remove endogenous PMN. Absolute numbers of granulocytemonocyte progenitor cells (CFU-C) and net endogenous colony-stimulating activity (CSA) production were found to be increased 3 days after cyclophosphamide in the bone marrow and 6 days after in the spleen. Administration of PMN extract to the drug-treated mice prior to rebound granulopoiesis substantially decreased CSA production and CFU-C but not spleen B lymphocyte colony-forming cells. In addition, mice treated with PMN extract had decreased levels of CSA in serum and in conditioned medium of marrow-free bone, heart, and lung cultures. Inhibition was reversed by injection of bacterial lipopolysaccharide. Extracts from PMN of patients with chronic myelogenous leukemia, inactive in vitro, had no effect in vivo. These results demonstrate that inhibitory activity derived from PMN can control granulopoiesis in vivo.
Insights
Human neutrophil extracts inhibit the recovery of granulopoiesis after chemotherapy. Neutrophil extracts reduced key blood cell precursors and colony-stimulating activity, demonstrating their role in controlling granulopoiesis.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Cyclophosphamide treatment depletes endogenous neutrophils, leading to rebound granulopoiesis.
- Neutrophils play a role in regulating hematopoiesis, particularly granulopoiesis.
- Colony-stimulating activity (CSA) is crucial for the production of granulocytes.
Purpose of the Study:
- To investigate the inhibitory effect of cell-free extracts from human polymorphonuclear neutrophils (PMN) on rebound granulopoiesis in mice.
- To determine the impact of PMN extracts on progenitor cell numbers and CSA production following chemotherapy.
Main Methods:
- Mice were pretreated with cyclophosphamide to induce neutropenia and subsequent rebound granulopoiesis.
- Cell-free extracts from human PMN were administered to the treated mice.
- Levels of granulocyte-monocyte progenitor cells (CFU-C), CSA, and other immune cell populations were assessed.
Main Results:
- PMN extracts significantly inhibited rebound granulopoiesis, reducing CFU-C numbers and CSA production.
- The inhibitory effect was observed in both bone marrow and spleen.
- CSA levels in serum and conditioned media were decreased, and inhibition was reversed by bacterial lipopolysaccharide.
- Extracts from chronic myelogenous leukemia (CML) PMN, which were inactive in vitro, showed no effect in vivo.
Conclusions:
- Cell-free extracts from human PMN possess inhibitory activity that can control granulopoiesis in vivo.
- PMN-derived inhibitory factors play a significant role in regulating the recovery of granulopoiesis after cytotoxic drug treatment.
- This finding has implications for understanding neutrophil function in hematopoiesis and potential therapeutic strategies.