-
Seminars in Fetal & Neonatal Medicine Aug 2007The growth factors erythropoietin and granulocyte-colony stimulating factor have hematopoietic and non-hematopoietic functions. Both are used clinically in their... (Review)
Review
The growth factors erythropoietin and granulocyte-colony stimulating factor have hematopoietic and non-hematopoietic functions. Both are used clinically in their recombinant forms. Both also have interesting tissue-protective effects in other organs, which are unrelated to their hematopoietic functions. They have clinical hematopoietic uses in neonatal populations and in experimental non-hematopoietic research, and clinical potential as neuroprotective or tissue-protective agents.
Topics: Animals; Central Nervous System; Clinical Trials as Topic; Erythroid Precursor Cells; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Humans; Neuroprotective Agents; Recombinant Proteins
PubMed: 17321813
DOI: 10.1016/j.siny.2007.01.015 -
Experimental Parasitology Dec 2022The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma...
The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.
Topics: Humans; Trypanocidal Agents; Trypanosoma brucei brucei; HL-60 Cells
PubMed: 36273616
DOI: 10.1016/j.exppara.2022.108414 -
Journal of Immunology (Baltimore, Md. :... Oct 2008Blood neutrophil counts are determined by the differentiation and proliferation of precursor cells, the release of mature neutrophils from the bone marrow, margination,... (Review)
Review
Blood neutrophil counts are determined by the differentiation and proliferation of precursor cells, the release of mature neutrophils from the bone marrow, margination, trafficking and transmigration through the endothelial lining, neutrophil apoptosis, and uptake by phagocytes. This brief review summarizes the regulation of blood neutrophil counts, which is in part controlled by G-CSF, IL-17, and IL-23. Neutrophils are retained in the bone marrow through interaction of CXCL12 with its receptor CXCR4. The relevance of this mechanism is illustrated by rare diseases in which disrupting the desensitization of CXCR4 results in failure to release mature neutrophils from bone marrow. Although blood neutrophil numbers in inbred mouse strains and individual human subjects are tightly controlled, their large variation among outbred populations suggests genetic factors. One example is benign ethnic neutropenia, which is found in some African Americans. Reduced and elevated neutrophil counts, even within the normal range, are associated with excess all-cause mortality.
Topics: Animals; Bone Marrow; Cell Movement; Cell Proliferation; Chemokine CXCL12; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Humans; Interleukin-17; Interleukin-23; Leukocyte Count; Mice; Neutropenia; Neutrophils; Receptors, CXCR4
PubMed: 18832668
DOI: 10.4049/jimmunol.181.8.5183 -
Molecules (Basel, Switzerland) Jun 2022Quinolinones have been known for a long time as broad-spectrum synthetic antibiotics. More recently, the anticancer potential of this group of compounds has been...
Quinolinones have been known for a long time as broad-spectrum synthetic antibiotics. More recently, the anticancer potential of this group of compounds has been investigated. Following this direction, we obtained a small library of 3-methylidene-1-sulfonyl-2,3-dihydroquinolin-4(1)-ones with various substituents at positions 1, 2, 6, and 7 of the quinolinone ring system. The cytotoxic activity of the synthesized analogs was tested in the MTT assay on two cancer cell lines in order to determine the structure-activity relationship. All compounds produced high cytotoxic effects in MCF-7, and even higher in HL-60 cells. 2-Ethyl-3-methylidene-1-phenylsulfonyl-2,3-dihydroquinolin-4(1)-one, which was over 5-fold more cytotoxic for HL-60 than for normal HUVEC cells, was selected for further tests. This analog was shown to inhibit proliferation and induce DNA damage and apoptosis in HL-60 cells.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Molecular Structure; Quinolones; Structure-Activity Relationship
PubMed: 35684532
DOI: 10.3390/molecules27113597 -
Scientific Reports Apr 2022Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear...
Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear leukocyte (PMN), are the first cells to be activated during inflammation and subsequently migrate toward an injured tissue or infection site. This response is dependent on both biochemical signaling and the extracellular environment, one aspect of which includes increased temperature in the tissues surrounding the inflammation site. In our study, we analyzed temperature-dependent neutrophil migration using differentiated HL-60 cells. The migration speed of differentiated HL-60 cells was found to correlate positively with temperature from 30 to 42 °C, with higher temperatures inducing a concomitant increase in cell detachment. The migration persistence time of differentiated HL-60 cells was higher at lower temperatures (30-33 °C), while the migration persistence length stayed constant throughout the temperature range. Coupled with the increased speed observed at high temperatures, this suggests that neutrophils are primed to migrate more effectively at the elevated temperatures characteristic of inflammation. Temperature gradients exist on both cell and tissue scales. Taking this into consideration, we also investigated the ability of differentiated HL-60 cells to sense and react to the presence of temperature gradients, a process known as thermotaxis. Using a two-dimensional temperature gradient chamber with a range of 27-43 °C, we observed a migration bias parallel to the gradient, resulting in both positive and negative thermotaxis. To better mimic the extracellular matrix (ECM) environment in vivo, a three-dimensional collagen temperature gradient chamber was constructed, allowing observation of biased neutrophil-like differentiated HL-60 migration toward the heat source.
Topics: Cell Movement; HL-60 Cells; Humans; Inflammation; Neutrophils; Temperature
PubMed: 35488042
DOI: 10.1038/s41598-022-10858-w -
Oncology (Williston Park, N.Y.) Jul 2012The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the... (Review)
Review
The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the most curable subtype of acute myeloid leukemia (AML). Patients who do not survive generally succumb within the first 30 days after presentation or diagnosis, often from intracranial or pulmonary hemorrhage caused by the characteristic coagulopathy associated with this disease. For the majority of patients who avoid hemorrhagic complications, the goals of decreasing the side effects of diagnosis and treatment-including pain, inpatient hospital days, and late sequelae of cytotoxic chemotherapy-have emerged as paramount. Here, we discuss novel and provocative observations regarding diagnostic and treatment strategies for APL that are likely to emerge as standards of care in the next 5 years, and that may improve the rate of early hemorrhagic death and decrease diagnosis- and treatment-related morbidity.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Arsenic Trioxide; Arsenicals; Biopsy, Fine-Needle; Bone Marrow; Clinical Trials as Topic; Dexamethasone; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Oxides; Practice Guidelines as Topic; Prognosis; Pulmonary Edema; Remission Induction; Respiratory Insufficiency; Tretinoin
PubMed: 22888564
DOI: No ID Found -
Nature Jun 2020Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and...
Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and disease, accurate models for molecular dissection are required; however, the rapid expansion of transcriptional populations identified through single-cell analyses presents a major challenge for accurate comparisons between mutant and wild-type cells. Here we generate mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the GFI1 transcription factor. To determine the effects of SCN mutations, we generated single-cell references for granulopoietic genomic states with linked epitopes, aligned mutant cells to their wild-type equivalents and identified differentially expressed genes and epigenetic loci. We find that GFI1-target genes are altered sequentially, as cells go through successive states of differentiation. These insights facilitated the genetic rescue of granulocytic specification but not post-commitment defects in innate immune effector function, and underscore the importance of evaluating the effects of mutations and therapy within each relevant cell state.
Topics: Animals; Candida albicans; Cell Lineage; DNA-Binding Proteins; Disease Models, Animal; Female; Granulocyte Precursor Cells; Humans; Immunity, Innate; Male; Mice; Mice, Transgenic; Mutation; Neutropenia; Neutrophils; Transcription Factors
PubMed: 32494068
DOI: 10.1038/s41586-020-2227-7 -
Nutrients Jul 2023Unripe (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2...
Unripe (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2 inflammation and airway hyperresponsiveness in animal models of eosinophilic asthma. EA is metabolized by the gut microbiota to urolithin A (UA), which exhibits anti-inflammatory properties. However, it remains unclear whether uRO, EA, and UA reduce inflammatory responses and oxidative stress in respiratory epithelial cells and neutrophils. In this study, inflammation was induced in A549 (human lung epithelial cells) and dHL-60 cells (neutrophil-like cells differentiated from human promyelocytic leukemia HL-60 cells) and treated with various concentrations of water extract of uRO (uRO-w), EA, and UA. EA, uRO-w and UA suppressed the inflammatory cytokine and chemokine levels and reduced the expression of matrix metalloproteinase-9 in A549 cells stimulated with IL-1β. As a result of analyzing the mechanism by which these inflammatory molecules are expressed, it was found that EA, uRO-w, and UA regulated corticosteroid-sensitive mitogen activated protein kinase, nuclear factor κB, and corticosteroid-insensitive AKT. In addition, uRO-w, EA, and UA significantly reduced reactive oxygen species levels in phorbol 12-myristate 13-acetate-stimulated dHL-60 cells and inhibited neutrophil extracellular trap formation. Therefore, our results suggest that uRO-w, EA, and UA are potential therapeutic agents for preventing and treating inflammatory respiratory diseases.
Topics: Animals; Humans; HL-60 Cells; Ellagic Acid; Rubus; A549 Cells; Inflammation
PubMed: 37571300
DOI: 10.3390/nu15153364 -
General Pharmacology Jan 19961. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine... (Review)
Review
1. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and can be differentiated into neutrophilic or monocytic cells. 2. HL-60 cells express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- and platelet-activating factor receptors, receptors for purine and pyrimidine nucleotides, histamine H1- and H2-receptors, beta 2-adrenoceptors and prostaglandin receptors. 3. The major G-proteins in HL-60 cells are pertussis toxin (PTX)-sensitive Gi-proteins (Gi2 > Gi3). Gs-proteins and G-proteins of the Gq-family (e.g., G16) are expressed, too. 4. G-protein-regulated effector systems in HL-60 cells are adenylyl cyclase and phospholipase C-beta 2 (PLC-beta 2) and, possibly, phospholipase D (PLD), nonselective cation (NSC) channels and NADPH oxidase. 5. The expression of signal transduction pathways in HL-60 cells strongly depends on the differentiation state of cells. 6. Formyl peptides, via Gi-proteins, mediate activation of PLC, PLD, NSC channels, NADPH oxidase and azurophilic granule release and are referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)-differentiated HL-60 cells, C5a and LTB4 are partial and incomplete secretagogues, respectively. There are substantial differences in the Gi-protein activations induced by formyl peptides, C5a and LTB4. 7. In HL-60 promyelocytes, purine and pyrimidine nucleotides mediate activation of PLC and NSC channels largely via PTX-insensitive G-proteins and induce functional differentiation. In Bt2cAMP-differentiated HL-60 cells, they additionally activate PLD, NADPH oxidase and granule release via PTX-sensitive and -insensitive pathways. ATP and UTP are partial secretagogues. Multiple types of receptors (i.e., P2Y- and P2U-receptors and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8. Bt2cAMP- and 1 alpha,25-dihydroxycholecalciferol-differentiated HL-60 cells express H1-receptors coupled to Gi-proteins and PTX-insensitive G-proteins. In the former cells, histamine mediates activation of PLC and NSC channels, and in the latter, activation of NSC channels. Histamine is an incomplete secretagogue in these cells. 9. HL-60 promyelocytes express H2-receptors coupled to adenylyl cyclase, PLC, and NSC channels. There are substantial differences in the agonist/antagonist profiles of H2-receptor-mediated cAMP formation and rises in cytosolic Ca2+ concentration, indicative of the involvement of different H2-receptor subtypes. H2-receptors mediate functional differentiation of HL-60 cells. 10. Certain cationic-amphiphilic histamine receptor ligands (i.e., 2-substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl-toluidide derivative) show stimulatory effects in HL-60 cells that are attributable to receptor-independent activation of Gi-proteins.
Topics: Antigens, CD; Calcium Channels; GTP-Binding Proteins; HL-60 Cells; Humans; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Membrane Glycoproteins; Receptor, Anaphylatoxin C5a; Receptors, Cell Surface; Receptors, Complement; Receptors, Formyl Peptide; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Immunologic; Receptors, Peptide; Receptors, Purinergic; Signal Transduction
PubMed: 8742493
DOI: 10.1016/0306-3623(95)00107-7 -
PloS One 2023In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In...
OBJECTIVES
In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS.
METHODS
We performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS).
RESULTS
CD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7.
CONCLUSIONS
Myeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.
Topics: Humans; Granulocyte Precursor Cells; Immunophenotyping; Megakaryocyte Progenitor Cells; Retrospective Studies; Antigens, CD34; Myelodysplastic Syndromes
PubMed: 37729123
DOI: 10.1371/journal.pone.0291662