Differentiation of Bone Marrow Macrophage Precursors from Mouse under the Influence of Interleukin-2, Are Interleukin-2 Activated Macrophage Precursors Natural Killer (NK-) Cells ?

Abstract

It is well known that NK cells (natural killer cells) play an important role in the natural defense of immune system against neoplastic or virally infected cells, as well as certain microorganisms. Nevertheless, the cell lineage of NK cells has not yet been clarified. In the present work the bone-marrow precursor cells, which could differentiate into NK cells after activating with interleukin-2 (NK cytotoxicity stimulation), were studied under the bone marrow culture conditions. It was found out that these NK cell precursors from bone marrow were dependent on myeloid growth factors: GM-CSF (granulocyte-macrophage colony-stimulating factor) or CSF-1 (colony-stimulating factor 1, i.e. macrophage colony-stimulating factor), to proliferate. Incubating these NK cell precursors only with CSF-1 or PMA (phorbol 12-myristate 13-acetate), the factor which stimulates the cell differentiation, the cells developed into typical mature macrophages in a short time (24-72 hours). Thus, these bone marrow precursor cells, which were able to differentiate into NK cells, were identified as macrophage precursors.

Interleukin-2 is the crucial factor that influences the differentiation of bone marrow macrophage precursors into the direction to NK cells. Within 3-6 days of incubation with interleukin-2, these macrophage precursor cells developed first into NK cells and then into LAK cells (lymphokine-activated killer cells) which have been well known as the further activated form of NK cells. The cell types were determined by morphological, phenotypic, and functional investigations.

The experimental results presented in this work demonstrate that NK/LAK cells might derive from macrophage system.