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Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and their precursors
H Biermann1, B Pietz, R Dreier
1Institute of Experimental Dermatology, University of Münster, Germany.
Abstract:
Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM; approximately 50% of BM cells), in peripheral blood (PB), and in inflammatory infiltrates of mice, but also in humans during myeloproliferative disorders. They are usually referred to as polymorphonuclear cells (PMN), but we demonstrate that they additionally encompass different types of mononuclear (MNC)-like ring cells. PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center and were sorted among the GR-1high fraction. The MNC-like ring cells belonged to the GR-1low fraction. Their nuclei 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-HR3), activity of unspecific esterase, and phagocytosis of Leishmania major. A second subgroup contained myeloic precursor cells as they proliferated (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of peroxidase activity compatible with myelocytes, promyelocytes, or promonocytes. A third subgroup of cells had large, sometimes lobulated nuclei, was lineage 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 cells encompassed mainly PMN, but also monocytes and cells with characteristics of both the granulocytic and monocytic lineage. Thus, ring cells comprise mature and precursor forms of myeloic cells. Their analysis revealed that in mice a clear distinction between the granulocytic and monocytic lineage beyond the GM-CFU stage is not always feasible.
Insights
Ring cells, leukocytes with unique nuclei, include polymorphonuclear cells and diverse mononuclear-like cells. These myeloid cells, found in bone marrow and blood, challenge lineage distinctions in mice.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Leukocytes with ring-shaped nuclei, termed ring cells, are observed in bone marrow, peripheral blood, and inflammatory sites in mice and humans with myeloproliferative disorders.
- These cells are typically identified as polymorphonuclear cells (PMN), but this study investigates a broader classification.
Purpose of the Study:
- To characterize the diverse cell types encompassed by the term "ring cells."
- To differentiate between polymorphonuclear (PMN) and mononuclear (MNC)-like ring cells.
- To explore the myeloid lineage relationships of these cells in mice.
Main Methods:
- Cell sorting based on GR-1 expression (GR-1high and GR-1low fractions).
- Ultrastructural analysis, immunophenotyping (BM8, F4/80, CD13, ER-HR3, ER-MP12), and functional assays (esterase activity, phagocytosis).
- Analysis of proliferation markers (Ki67) and stem cell markers (c-kit, sca-1).
Main Results:
- Ring cells include PMN with constricted nuclei and MNC-like cells with unsegmented nuclei.
- MNC-like ring cells comprise monocytes/macrophages, myeloid precursors (myelocytes, promyelocytes, promonocytes), and cells closely related to hematopoietic stem cells.
- Peripheral blood ring cells consist mainly of PMN, but also monocytes and mixed granulocytic/monocytic lineage cells.
Conclusions:
- Ring cells represent a heterogeneous population of mature and precursor myeloid cells.
- The study highlights that distinguishing between granulocytic and monocytic lineages beyond the granulocyte-macrophage colony-forming unit (GM-CFU) stage in mice is not always definitive.
- Ring cell morphology provides insights into myeloid cell differentiation and plasticity.