Constitutive Host Resistance
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
The mononuclear and polymorphonuclear phagocytes are produced in the bone marrow from a common stem cell (Figure 3.3). The stem cells committed to produce polymorphonuclear leukocytes differentiate into myeloblasts, and those that will produce mononuclear phagocytes differentiate into monoblasts. The sequence for polymorphonuclear leukocyte differentiation requires four cell divisions; each results in a progressive decrease in cell size and an increase in nuclear compaction. The compact nucleus ultimately assumes the characteristic polymorphonudear shape. The myeloblast gives rise to promyelocytes that divide to produce first myelocyte I cells, then myelocyte II cells. The myelocyte II cells give rise to metamyelocytes. Following the production of the metamyelocyte, no further cell division occurs. The metamyelocytes develop into band cells that become segmented cells and, finally, mature polymorphonuclear leukocytes as they leave the bone marrow and enter the blood. Under conditions of stress, such as is caused by infection, immature forms such as band cells may enter the blood.
Chronic Myeloid Leukemia
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
The BM aspirate (Figure 27.3) is hypercellular with an increased M:E ratio due to both myeloid hyperplasia and erythroid hypoplasia (myeloid-to-erythroid ratio is usually from 10:1 to 30:1). Granulocytic cells show full maturation to segmented forms with a leftward shift and a peak (myelocyte bulge) in the percentage of myelocytes. Erythroid and granulocytic series do not exhibit overt dyspoiesis. Megakaryocytes may be increased in number and display atypia, most characteristically in the form of smaller cells with centrally located hypolobated nucleus [they differ from hypolobated micromegakaryocytes seen in myelodysplastic syndrome (MDS) with del(5q)]. In the CP, blasts do not exceed 5% of the marrow cells. Eosinophils and basophils are increased in number. Scattered sea-blue histiocytes may be present (pseudo-Gaucher cell; storage histiocytes).
Inflammation
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
In some forms of chronic granulocytic leukemia, neutrophil production and maturation are stopped at the myelocyte stage, and thus large numbers of immature cells are present in the bloodstream. Since these cells are morphologically and functionally immature, individuals suffering from this disorder have increased susceptibility to infections.52 The high susceptibility to certain forms of bacterial sepsis of the renal medulla is connected with a delayed or inadequate influx of neutrophils during the inflammatory response. High salt concentration in the peritubular fluid or ammonia produced in the kidney may impair the migratory or phagocytic capacity of neutrophils.70,386 Membrane fluidizers can affect the number and affinity of chemotactic receptors on polymorphonuclear leukocytes.454 Chemotactic peptides induce changes in the cytosolic Ca2+ content of neutrophils from patients with chronic granulomatous disease.272 Threadworm infection causes intense cellular responses in humans.141
Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst
Published in Journal of Immunotoxicology, 2023
Drake W. Phelps, Anika I. Palekar, Haleigh E. Conley, Giuliano Ferrero, Jacob H. Driggers, Keith E. Linder, Seth W. Kullman, David M. Reif, M. Katie Sheats, Jamie C. DeWitt, Jeffrey A. Yoder
Continuous DMSO treatment of HL-60 cells induced cytomorphological features of neutrophil myeloid differentiation and maturation (Supplemental Figure S(10)). Undifferentiated HL-60 cells retained an immature phenotype, and 100% of cells had features of promyelocytes, an immature stage of myeloid differentiation. Cells were in a proliferative state and mitotic figures were present (average 7/300; 2.3%). In contrast, DMSO treatment induced neutrophilic, myeloid differentiation in HL-60 cells. All cells were more mature, displaying features of myelocyte, metamyelocyte, band neutrophil, or mature neutrophil morphology. The cells were smaller and had smaller nuclei that, in more mature cells, had nearly absent mitotic figures (0.3/300; 0.1%). DMSO withdrawal from neutrophil-like HL-60 cells was associated with a return to promyelocyte morphology and to mitotic activity (average 5/300; 1.7%) that was more similar to untreated cells, indicating that continued DMSO exposure was needed to main myeloid differentiation in HL-60 cells.
CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives
Published in Expert Review of Clinical Immunology, 2019
Tabata T. França, Lucila A. Barreiros, Basel K. al-Ramadi, Hans D. Ochs, Otavio Cabral-Marques, Antonio Condino-Neto
The neutropenia in CD40L deficiency has been attributed to maturation arrest of the myeloid lineage at the promyelocyte-myelocyte stage [14,26], suggesting a pivotal role of CD40L–CD40 interaction during neutrophils development. A possible explanation for the neutropenia presented by patients with CD40L deficiency is that CD40L–CD40 interaction in the bone marrow stimulates the synthesis of G-CSF, which induces maturation and release of neutrophils into the peripheral blood [7]. It has been hypothesized that the absence of CD40L impairs the local production of G-CSF, resulting in severe neutropenia [77], but the pathophysiologic mechanisms can be broader and remain to be investigated. Supporting this idea, the administration of recombinant human G-CSF (rhG-CSF) improves the neutrophil count and decreases the occurrence of infections.
Chemoprotection by Kolaviron of Garcinia kola in Benzene-induced leukemogenesis in Wistar rats
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Olaniyi Solomon Ola, Esther Oladayo Ogunkanmbi, Emmanuel Babatife Opeodu
Myelodysplasia has been suggested to be a significant step in the generation of leukemia by benzene [36]. Benzene metabolite hydroquinone was earlier reported to promote proliferation and differentiation of the myeloblast into the myelocyte stage but inhibited the maturation of myelocyte into neutrophil [44]. The mutation of the clone of myelocytes without subsequent DNA repair may be further proliferated and promote the development of leukemia [45]. Reactive metabolites generated during benzene biotransformation can induce genotoxicity and cytotoxicity through diverse mechanisms [46–48]. The study had reported involvement of benzoquinones and other benzene reactive oxygen metabolites in the induction of oxidative DNA damage, lipid peroxidation and strand breaks in the DNA of bone marrow cells in benzene-induced toxicity [49–51]. The result of this study indicated the significant induction of clastogenicity in the marrow of the rats exposed to benzene as shown by generation of significantly high occurrence of micronucleated polychromatic erythrocyte in the marrow of leukemic rats. However, administration of kolaviron significantly ameliorated the benzene-induced clastogenicity in the leukemic rats.
Related Knowledge Centers
- Cytoplasm
- Myeloblast
- Peroxidase
- Promyelocyte
- Granulocyte
- Bone Marrow
- Blood
- Cell
- Basophilic
- Specific Granule