Multipotentiality of Human Mature Blood Cells

Abstract

We found a lineage switch of human postmitotic neutrophils into macrophages in culture. When CD¹⁵ CD14^-cells, the majority of which are band neutrophils, were cultured with GM-CSF, TNF-α, IFN-γ, and IL-4, and subsequently with M-CSF, they obtained morphologic, cytochemical, phenotypic, genotypic, and functional features of macrophages. Postmitotic neutrophils can give rise to macrophages as well as polymorphonuclear neutrophils.GM-CSF and TGF-β1 are produced in the skin. Notch ligand Delta-1 is expressed by skin resident epidermal stem cells which are surrounded by keratinocytes. In the presence of GM-CSF, TGF-β1, and Notch ligand Delta-1, human blood CD 14⁺ monocytes differentiated into cells that had Langerhans cell markers : CDla, Langerin, cutaneous lymphocyte-associated antigen, CCR6, E-cadherin, and Birbeck granules. Blood monocytes become not only macrophages anddendritic cells but also Langerhans cells. These data suggest that human band neutrophils and monocytes, both of which are lineage-committed mature blood cells, retain the multipotentiality and are capable of generating more types of mature cells than is generally accepted.