scholarly journals THE KINETICS OF PROMONOCYTES AND MONOCYTES IN THE BONE MARROW

1970 ◽  
Vol 132 (4) ◽  
pp. 813-828 ◽  
Author(s):  
Ralph van Furth ◽  
Martina M. C. Diesselhoff-den Dulk
Keyword(s):  
Bone Marrow ◽  
Cell Types ◽  
Mononuclear Phagocytes ◽  
Blood Monocytes ◽  
Proliferating Cells ◽  
Synthesis Time ◽  
In Vivo Labeling ◽  
The Mean

The mononuclear phagocytes of the bone marrow can be classified into two cell types, promonocytes and monocytes. The present study was performed to establish whether the promonocytes are the progenitors of the monocytes and to determine the kinetic characteristics of the promonocytes and monocytes in the bone marrow compartment. Both in vitro labeling studies with thymidine-3H and determination of the relative amount of DNA in the nuclei of individual cells showed that under normal steady-state conditions the promonocytes are proliferating cells and the monocytes, nondividing cells. In vivo labeling studies provided further evidence that the promonocytes are the progenitor cells of the monocytes. During the first 24 hr after labeling, the promonocytes showed a constant high level of labeling (about 70%). The mean grain count of these cells decreased with time. The labeling index of the monocytes of the bone marrow increased during the first 24 hr after in vivo labeling, but during the same period the mean grain counts remained almost constant, with values amounting to about half those of the promonocytes during the first 6 hr of the experiment. The data concerning the labeling indices and the percentage distribution ratio of the promonocytes and monocytes in the bone marrow, and the labeling indices of the peripheral blood monocytes are used to construct a model population. The results lead to the conclusions that the promonocytes are multiplicative cells and that both daughter cells arising from the division of a promonocyte are monocytes. The DNA-synthesis time found for the promonocytes is 13.6 hr. From this value, the average generation time was computed to be 19.5 hr.

scholarly journals Characteristics of human mononuclear phagocytes

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 485-500 ◽  
Author(s):  
R van Furth ◽  
JA Raeburn ◽  
TL van Zwet
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Blood Monocytes ◽  
Surface Receptors ◽  
Three Body

Abstract In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80% of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.

scholarly journals Proliferative characteristics of monoblasts grown in vitro.

1975 ◽  
Vol 142 (5) ◽  
pp. 1200-1217 ◽  
Author(s):  
T J Goud ◽  
R van Furth
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Colony Size ◽  
Cell Types ◽  
Mononuclear Phagocyte ◽  
Culture Technique ◽  
Mononuclear Phagocytes ◽  
Synthesis Time

In a previous study also done with a liquid culture technique, the monoblast was identified and characterized as the most immature cell of the mononuclear phagocyte cell line recognized so far. The present study concerned the proliferative behavior of the monoblast and promonocyte in colonies. The cell-cycle times of both cell types were determined on the basis of four independent methods. The resulting values all show excellent agreement: for the monoblast 11.0-11.9 h, and for the promonocyte 11.4-12.8 h. The DNA-synthesis time found for the two cell types amounted to 5.7 h for the monoblast and 5.5 h for the promonocyte. The duration of the other phages of the cell cycle of the proliferating mononuclear phagocytes proved to be: G2 phase, 0.6 h; mitosis phage, 1.8 h; and G1 phase, 3.5-3.8 h. The individual colonies showed a biphasic pattern of colony growth, an initial phase of rapid proliferation being followed by a stage wtih a markedly decreased growth rate. In the initial stage only monoblasts are present in the colony; when the growth rate slows down promonocytes and macrophages appear. These observations support the earlier conclusion that the monoblast is without doubt the precursor of the promonycyte. Colony size was found to vary widely. The main factor underlying this variation proved to be the lag time between the start of the culture and the time point at which the colony-forming cells begin to divide. Mathematical analysis showed that the variation in colony size probably does not arise from heterogeneity of the population of colony-forming cells. A mathematical approach was used to determine the proportion of self-replicating and differentiating cells among the dividing monoblasts and promonocytes in the colony. The results indicate that initially in vitro the majority of the cells of both types are self-replicating cells, but later an increasing proportion of the dividing cells give rise to another, more mature type of cell. On the basis of the conclusion that the monoblast initiates the mononuclear phagocyte colony, the number of monoblasts (2.5 X 10(5)) present in vivo was estimated to be half the number of the promonocytes. In view of this ratio the mostly likely pattern for the proliferation of mononuclear phagocytes in the bone marrow is that a monoblast divides once, giving rise to two promonocytes which in their turn divide once and form two nonproliferating monocytes.

scholarly journals Characteristics of human mononuclear phagocytes

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 485-500 ◽  
Author(s):  
R van Furth ◽  
JA Raeburn ◽  
TL van Zwet
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Blood Monocytes ◽  
Surface Receptors ◽  
Three Body

In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80% of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.

scholarly journals In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes.

1982 ◽  
Vol 156 (6) ◽  
pp. 1604-1614 ◽  
Author(s):  
E H Burger ◽  
J W Van der Meer ◽  
J S van de Gevel ◽  
J C Gribnau ◽  
G W Thesingh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Electron Microscopic Examination ◽  
Osteoclast Formation ◽  
Mononuclear Phagocytes ◽  
Long Bone ◽  
Embryonic Liver ◽  
Blood Monocytes ◽  
Electron Microscopic ◽  
Embryonic Mouse

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.

MicroRNA Expression in Macrophages-Derived Microvesicles May Contribute to Cellular Survival and Differentiation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3557-3557
Author(s):  
Noura Ismail ◽  
Clay B. Marsh ◽  
Melissa Hunter
Keyword(s):  
Peripheral Blood ◽  
Cell Types ◽  
Microrna Expression ◽  
Mononuclear Phagocytes ◽  
Blood Monocytes ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Differentiated Cells ◽  
Numerous Cell

Abstract Microvesicles (MV) (also know as exosomes) are small membrane-bound vesicles released by numerous cell types that contain proteins, mRNA and microRNA. We found that MV from activated monocytes drove survival and differentiation in naïve cells. We therefore were interested in understanding the content of MV produced by activated mononuclear phagocytes. Purified peripheral blood monocytes were treated in vitro for 24 h with or without the monocyte survival factors, GM-CSF or M-CSF, respectively. Examination of monocytes and macrophages by electron microscopy or culture supernatants by flow cytometry demonstrated that monocytes produced MV, which quantitatively increased upon differentiation. Treatment with GM-CSF resulted in more MV production than M-CSF-treated monocytes. To examine whether MV from differentiated cells induced myeloid maturation, the MV were collected and added to fresh monocytes; only MV derived from GM-CSF treated cells induced differentiation of naïve monocytes into macrophages. We next hypothesized that expression of microRNA contained in the MV modulated differentiation of monocytes. Profiling of MV from GM-CSF and M-CSF derived macrophages revealed only two significantly expressed microRNAs. We found that mir-155 was significantly elevated by two-fold in MV from GM-CSF-treated cells, while mir-340 was significantly increased seven-fold in M-CSF-derived MV. Notably, mir- 223 was the highest expressed microRNA in MV from both GM-CSF and M-CSF-treated cells. Recent data suggest that expression of mir-223 regulates myeloid, granulocytic and osteoclasts differentiation, and has a role in hematopoietic stem cell proliferation. While mir-223 is present in MV from both GM-CSF and M-CSF treated cells, it is possible that the low abundance of MV produce from M-CSF-treated cells resulted in less effective concentration to induce differentiation. In this model, it is also possible that regulation of proteins targeted by the increase in mir-155 and decrease mir-340 in the GM-CSF-derived MV are responsible for myeloid differentiation. Since changes in microRNA expression including mir-223 has been reported in AML, our data suggest that myeloid-derived MV in the peripheral blood containing mir-223 may be altered contributing to leukemogenesis.

scholarly journals Microglial mitogens are produced in the developing and injured mammalian brain.

1991 ◽  
Vol 112 (2) ◽  
pp. 323-333 ◽  
Author(s):  
D Giulian ◽  
B Johnson ◽  
J F Krebs ◽  
J K George ◽  
M Tapscott
Keyword(s):  
Cerebral Cortex ◽  
Growth Factors ◽  
Molecular Mass ◽  
Inflammatory Responses ◽  
Mononuclear Phagocytes ◽  
Mammalian Brain ◽  
Blood Monocytes ◽  
Adult Rats

The central nervous system produces growth factors that stimulate proliferation of ameboid microglia during embryogenesis and after traumatic injury. Two microglial mitogens (MMs) are recovered from the brain of newborn rat. MM1 has an approximate molecular mass of 50 kD and a pI of approximately 6.8; MM2 has a molecular mass of 22 kD and a pI of approximately 5.2. These trypsin-sensitive proteins show specificity of action upon glia in vitro serving as growth factors for ameboid microglia but not astroglia or oligodendroglia. Although the MMs did not stimulate proliferation of blood monocytes or resident peritoneal macrophage, MM1 shows granulocyte macrophage colony-stimulating activity when tested upon bone marrow progenitor cells. Microglial mitogens may help to control brain mononuclear phagocytes in vivo. The MMs first appear in the cerebral cortex of rat during early development with peak levels around embryonic day E-20, a period of microglial proliferation. Microglial mitogens are also produced by traumatized brain of adult rats within 2 d after injury. When infused into the cerebral cortex, MM1 and MM2 elicit large numbers of mononuclear phagocytes at the site of injection. In vitro study shows that astroglia from newborn brain secrete MM2. These observations point to the existence of a regulatory system whereby secretion of proteins from brain glia helps to control neighboring inflammatory responses.

Meis1-mediated apoptosis is caspase dependent and can be suppressed by coexpression of HoxA9 in murine and human cell lines

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1222-1230 ◽  
Author(s):  
Peter J. Wermuth ◽  
Arthur M. Buchberg
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Selective Advantage ◽  
Myeloid Differentiation ◽  
Homeodomain Protein ◽  
Murine Bone Marrow ◽  
Differentiation Pathways

AbstractCoexpression of the homeodomain protein Meis1 and either HoxA7 or HoxA9 is characteristic of many acute myelogenous leukemias. Although Meis1 can be overexpressed in bone marrow long-term repopulating cells, it is incapable of mediating their transformation. Although overexpressing HoxA9 alone transforms murine bone marrow cells, concurrent Meis1 overexpression greatly accelerates oncogenesis. Meis1-HoxA9 cooperation suppresses several myeloid differentiation pathways. We now report that Meis1 overexpression strongly induces apoptosis in a variety of cell types in vitro through a caspase-dependent process. Meis1 requires a functional homeodomain and Pbx-interaction motif to induce apoptosis. Coexpressing HoxA9 with Meis1 suppresses this apoptosis and provides protection from several apoptosis inducers. Pbx1, another Meis1 cofactor, also induces apoptosis; however, coexpressing HoxA9 is incapable of rescuing Pbx-mediated apoptosis. This resistance to apoptotic stimuli, coupled with the previously reported ability to suppress multiple myeloid differentiation pathways, would provide a strong selective advantage to Meis1-HoxA9 coexpressing cells in vivo, leading to leukemogenesis.

scholarly journals Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes

2003 ◽  
Vol 161 (5) ◽  
pp. 945-956 ◽  
Author(s):  
Yoshito Takeda ◽  
Isao Tachibana ◽  
Kenji Miyado ◽  
Masatoshi Kobayashi ◽  
Toru Miyazaki ◽  
...  
Keyword(s):  
Complex Formation ◽  
Alveolar Macrophages ◽  
Bone Marrow Cells ◽  
Giant Cells ◽  
Mononuclear Phagocytes ◽  
Blood Monocytes ◽  
Multinucleated Cells ◽  
Infected Cells

Tetraspanins CD9 and CD81 facilitate the fusion between gametes, myoblasts, or virus-infected cells. Here, we investigated the role of these tetraspanins in the fusion of mononuclear phagocytes. Expression of CD9 and CD81 and their complex formation with integrins were up-regulated when blood monocytes were cultured under normal conditions. Under fusogenic conditions in the presence of Con A, CD9 and CD81 up-regulation was inhibited, and their complex formation with integrins was down-regulated. Anti-CD9 and -CD81 antibodies, which were previously shown to inhibit the fusion of gametes, myoblasts, and virus-infected cells, unexpectedly promoted the fusion of monocytes and alveolar macrophages. However, these effects were not due to altered cell adhesion, aggregation, or cytokine production. When stimulated in vitro or in vivo, alveolar macrophages and bone marrow cells of CD9- and CD81-null mice formed larger numbers of multinucleated cells than those of wild-type mice. Finally, CD9/CD81 double-null mice spontaneously developed multinucleated giant cells in the lung and showed enhanced osteoclastogenesis in the bone. These results suggest that CD9 and CD81 coordinately prevent the fusion of mononuclear phagocytes.

The G Protein-Coupled Receptor cysLT1 Mediates Gi Protein-Dependent Chemotaxis and Adhesion of CD34+ Cells in Vitro Similar to CXCR4, but Not Progenitor Mobilization in Vivo.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1388-1388
Author(s):  
Adriana Drost ◽  
Lena Jaggy ◽  
Lothar Kanz ◽  
Robert Möhle
Keyword(s):  
Bone Marrow ◽  
G Protein ◽  
Actin Polymerization ◽  
Cell Types ◽  
Mediated Effects ◽  
Cd34 Cells ◽  
Gi Protein ◽  
G Protein Coupled

Abstract CysLT1, which is expressed in several cell types during inflammation and allergy, and the homing related chemokine receptor CXCR4 both belong to the family of G protein-coupled receptors (GPCR). Similar to CXCR4, the cysteinyl-leukotriene receptor cysLT1 is strongly expressed in CD34+ cell lines and CD34+ hematopoietic progenitor cells (HPC). We therefore compared the effects mediated by cysLT1 on HPC to those observed after activation of CXCR4. The most potent cysLT1 ligand LTD4 induced chemotaxis and adhesion of CD34+ HPC to endothelial cells, immobilized VCAM-1 and fibronectin, which was comparable to effects induced by the CXCR4 ligand SDF-1. CysLT1- and CXCR4-mediated effects were inhibited by pertussis toxin (PTX), suggesting that both GPCRs employ the same Gi-protein-dependent signaling pathways in CD34+ HPC. This is supported by identical time courses of intracellular calcium fluxes and actin polymerization induced by LTD4 and SDF-1, as measured by time-dependent flow cytometry. Given the striking similarities of cysLT1- and CXCR4-mediated effects in vitro, one might expect also overlapping functions in vivo. We therefore investigated whether blocking of cysLT1 is associated with HPC mobilization. As cysLT1 antagonists are established for therapy and prophylaxis in patients with allergic and exercise-induced asthma, circulating CD34+ progenitors were enumerated after initiation of a treatment with the cysLT1 antagonist montelukast, used as asthma prophylaxis in otherwise healthy subjects. The number of CD34+ cells or white blood counts did not differ significantly from the baseline value 2, 4, 8, 12, and 24 hours after administration of 10 mg montelukast, in contrast to previous studies analyzing stem cell mobilization induced by CXCR4 antagonists. This corresponds with our in vitro findings that LTD4 is produced by bone marrow endothelium and stromal cells only when deprived of hematopoietic cells, in contrast to the constitutive production of SDF-1. We conclude that cysLT1 is not involved in bone marrow retention of HPC during steady-state hematopoiesis, but may modulate HPC homing when its ligands are produced either locally (i.e. bone marrow aplasia) or systemically (i.e. inflammation).

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