Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes,and their precursors

Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM; similar to 50% of BM cells), in peripheral blood (PB), and in inflamma tory infiltrates of mice, but also in humans during myeloproliferative diso rders. They are usually referred to as polymorphonuclear cells (PMN), but w e demonstrate that they additionally encompass different types of mononucle ar (MNC)-like ring cells. PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center and were sorted among the GR-1(high) fracti on. The MNC-like ring cells belonged to the GR-1(low) fraction. Their nucle i were not segmented and the cytoplasmic center of their nuclei was small. They were heterogeneous with one subgroup containing monocytes/macrophages according to ultrastructure, immunophenotype (BM8, F4/80, CD13, ER-HR13), a ctivity of unspecific esterase, and phagocytosis of Leishmania major. A sec ond subgroup contained myeloic precursor cells as they proliferated (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of p eroxidase activity compatible with myelocytes, promyelocytes, or promonocyt es, A third subgroup of cells had large, sometimes lobulated nuclei, was li neage marker(negative/low) (GR-1, Mac-1, B220 etc.), CD38(-), but c-kit(+) and sca-1(+), and thus belonged to a close progeny of murine hematopoietic stem cells. In PB, ring tells encompassed mainly PMN, but also monocytes an d cells with characteristics of both the granulocytic and monocytic Lineage . Thus, ring cells comprise mature and precursor forms of myeloic cells. Th eir analysis revealed that in mice a clear distinction between the granuloc ytic and monocytic lineage beyond the GM-CFU stage is not always feasible.