Sequential effects of lithium on haematopoiesis

Area of Science:

• Hematology
• Stem Cell Biology
• Pharmacology

Background:

• Lithium salts are known to increase blood neutrophil counts and stimulate colony-stimulating activity (CSA) in normal subjects.
• CSA is crucial for the growth of granulocyte-macrophage progenitor cells (CFU-GM).

Purpose of the Study:

• To investigate the hematopoietic changes induced by lithium administration in mice.
• To elucidate the effects of lithium on various stem and progenitor cell populations.

Main Methods:

• Mice were administered lithium chloride (LiCl) daily.
• Blood cell counts, serum CSA levels, and concentrations of various progenitor cells (CFU-GM, CFU-M, BFU-E, CFU-E, CFU-S, E-CFU) were assessed.

Main Results:

• Lithium administration led to increased blood neutrophils, platelets, and serum CSA levels.
• Preceding these increases were expanded marrow neutrophil production and elevated levels of CFU-GM, CFU-M, BFU-E, and CFU-E.
• A significant, sustained increase in transplantable pluripotential stem cells (CFU-S) was observed starting on day 2.
• The increase in CFU-S was not mirrored in endogenous stem cells (E-CFU), indicating a resistant stem cell subpopulation.

Conclusions:

• Lithium initially increases marrow CFU-S, either directly or indirectly.
• Subsequent increases in progenitor cells and CSA contribute to enhanced granulocyte production.
• Lithium's effect on stem cells involves a specific, responsive portion of the stem cell pool.