scholarly journals The origin, kinetics, and characteristics of the kupffer cells in the normal steady state

1978 ◽  
Vol 148 (1) ◽  
pp. 1-17 ◽  
Author(s):  
RW Crofton ◽  
MMC Diesselhoff-Den Dulk ◽  
RV Furth
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Kupffer Cells ◽  
Peritoneal Macrophages ◽  
Turnover Time ◽  
Mononuclear Phagocytes ◽  
Labeling Index ◽  
Cell Labeling ◽  
Initial Suspension

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.

scholarly journals THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES

1968 ◽  
Vol 128 (3) ◽  
pp. 415-435 ◽  
Author(s):  
Ralph van Furth ◽  
Zanvil A. Cohn
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Calf Serum ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
Sterile Inflammation

The origin and turnover of efferent populations of mouse mononuclear phagocytes has been described. Mononuclear phagocytes were defined as mononuclear cells which are able to adhere to glass and phagocytize. In vitro labeling studies with thymidine-3H showed that monocytes in the peripheral blood and peritoneal macrophages do not multiply and can be considered end cells in a normal, steady state situation. However, the mononuclear phagocytes of the bone marrow appear to be rapidly dividing cells. This conclusion was supported by in vivo labeling experiments. A peak of labeled mononuclear phagocytes of the bone marrow was found 24 hr after a pulse of thymidine-3H. This was followed, 24 hr later, by a peak of labeled monocytes in the peripheral blood. From these experiments it was concluded that the rapidly dividing mononuclear phagocytes of the bone marrow, called promonocytes, are the progenitor cells of the monocytes. Labeling studies after splenectomy and after X-irradiation excluded other organs as a major source of the monocytes. Peak labeling of both the blood monocyte and peritoneal macrophages occurred at the same time. A rapid entry of monocytes from the blood into the peritoneal cavity was observed, after a sterile inflammation was evoked by an injection of newborn calf serum. These data have led to the conclusion that monocytes give rise to peritoneal macrophages. No indications have been obtained that mononuclear phagocytes originate from lymphocytes. In the normal steady state the monocytes leave the circulation by a random process, with a half-time of 22 hr. The average blood transit time of the monocytes has been calculated to be 32 hr. The turnover rate of peritoneal macrophages was low and estimated at about 0.1% per hour. On the basis of these studies the life history of mouse mononuclear phagocytes was formulated to be: promonocytes in the bone marrow, → monocytes in the peripheral blood, → macrophages in the tissue.

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 Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes.

1979 ◽  
Vol 150 (1) ◽  
pp. 117-126 ◽  
Author(s):  
O Haller ◽  
H Arnheiter ◽  
J Lindenmann
Keyword(s):  
Bone Marrow ◽  
Influenza Virus ◽  
Marrow Cell ◽  
Peritoneal Macrophages ◽  
Influenza Viruses ◽  
Mononuclear Phagocytes ◽  
Lethal Challenge ◽  
Radiation Chimeras

Radiation chimeras produced by crosswise transfers of bone-marrow cell among histocompatible mice susceptible, or genetically resistant, to lethal challenge by a number of myxoviruses were used to test whether macrophage resistance (as assessed in vitro) and resistance of the animal (as measured in vivo), both previously shown to be brought about by the gene Mx, were causally related. 49 chimeras were tested individually, both of resistance of their macrophages to in vitro challenge with M-TUR (a strain of avian influenza virus A/Turkey/England/63 adapted to grow in cultured mouse peritoneal macrophages), and for resistance of the animal in vivo upon challenge with pneumotropic, neurotropic, or hepatotropic influenza viruses. Cultivated Kupffer cells and peritoneal macrophages harvested from chimeric mice expressed the resistance phenotype of the bone-marrow donor irrespective of the host environment in which they had differentiated. However, susceptibility or resistance in vivo was according to the genotype of the host. Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system.

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 Murine Kupffer cells. Mononuclear phagocytes deficient in the generation of reactive oxygen intermediates.

1985 ◽  
Vol 161 (5) ◽  
pp. 1079-1096 ◽  
Author(s):  
D A Lepay ◽  
C F Nathan ◽  
R M Steinman ◽  
H W Murray ◽  
Z A Cohn
Keyword(s):  
Kupffer Cells ◽  
Leishmania Donovani ◽  
Reactive Oxygen ◽  
Antigen Expression ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
High Yield ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates

Murine Kupffer cells (KC) were isolated by a high yield collagenase perfusion technique. The morphology, surface markers, and secretory products were typical of macrophages in other tissues. However, KC released negligible levels of H2O2 and O-2, in contrast to peritoneal macrophages. KC oxygen consumption was not increased by agents triggering a respiratory burst in peritoneal cells. Moreover, KC capacity to secrete reactive oxygen intermediates (ROI), in contrast to Ia antigen expression, was not enhanced by exposure to lymphokines or recombinant gamma interferon. The selective defect in KC oxidative response was paralleled by impaired in vitro killing of Toxoplasma gondii trophozoites and Leishmania donovani promastigotes and amastigotes. Deficient secretion of ROI by KC might protect hepatocytes and erythrocytes from injury during endocytosis by KC, but might render the liver more susceptible to parasitization by organisms that are primarily killed through oxygen-dependent mechanisms.

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.

scholarly journals Improved techniques for liquid culture of human and mouse bone marrow

Blood ◽  
1976 ◽  
Vol 47 (3) ◽  
pp. 369-379
Author(s):  
MJ Cline ◽  
DW Golde
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Large Scale ◽  
Membrane Surface ◽  
Diffusion Chamber ◽  
Mononuclear Phagocytes ◽  
Mouse Bone Marrow ◽  
Improved Performance ◽  
Proliferation In Vitro

Previous studies using the in vitro diffusion chamber (Marbrook) have shown that bone marrow grown in this system will undergo limited stem cell replication and differentiation to mature granulocytes and mononuclear phagocytes. A series of studies with modified culture systems was initiated to improve cell production and committed stem cell (CFU-C) proliferation in vitro. Introduction of a continuous-flow system and a migration technique providing means of egress for mature neutrophils resulted in substantially improved performance. CFU-C were found to be capable of migration through a 3-mu pore membrane. These studies indicated that membrane surface area, culture medium circulation, and mature cell egress were among the conditions that could be optimized for maximum hematopoietic cell proliferation in suspension culture. The present observations also suggested that large- scale in vitro growth of mammalian bone marrow may be feasible.

Behavior and Therapeutic Efficacy of β-Glucuronidase–Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2142-2150 ◽  
Author(s):  
Brian J. Freeman ◽  
Marie S. Roberts ◽  
Carole A. Vogler ◽  
Andrew Nicholes ◽  
A. Alex Hofling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Therapeutic Efficacy ◽  
Lysosomal Storage Diseases ◽  
Reticuloendothelial System ◽  
Mononuclear Phagocytes ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Mps Vii

Abstract Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted β-glucuronidase–positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of β-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

scholarly journals The immunosuppressant rapamycin blocks in vitro responses to hematopoietic cytokines and inhibits recovering but not steady-state hematopoiesis in vivo

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1543-1552 ◽  
Author(s):  
VF Quesniaux ◽  
S Wehrli ◽  
C Steiner ◽  
J Joergensen ◽  
HJ Schuurman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
T Cell ◽  
T Cell Response ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Hematopoietic Recovery ◽  
Stimulating Factor

Abstract The immunosuppressive drug rapamycin suppresses T-cell activation by impairing the T-cell response to lymphokines such as interleukin-2 (IL- 2) and interleukin-4 (IL-4). In addition, rapamycin blocks the proliferative response of cell lines to a variety of hematopoietic growth factors, including interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage- colony stimulating factor (GM-CSF), and kit ligand (KL), suggesting that it should be a strong inhibitor of hematopoiesis. In this report, we studied the effects of rapamycin on different hematopoietic cell populations in vitro and in vivo. In vitro, rapamycin inhibited the proliferation of primary bone marrow cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in cell-conditioned media. Rapamycin also inhibited the multiplication of colony-forming cells in suspension cultures containing IL-3 plus interleukin-1 (IL-1) or interleukin-11 (IL-11) plus KL. In vivo, treatment for 10 to 28 days with high doses of rapamycin (50 mg/kg/d, orally) had no effect on myelopoiesis in normal mice, as measured by bone marrow cellularity, proliferative capacity, and number of colony-forming progenitors. In contrast, the same treatment strongly suppressed the hematopoietic recovery normally seen 10 days after an injection of 5-fluorouracil (5- FU; 150 mg/kg, intravenously [i.v.]). Thus, rapamycin may be detrimental in myelocompromised individuals. In addition, the results suggest that the rapamycin-sensitive cytokine-driven pathways are essential for hematopoietic recovery after myelodepression, but not for steady-state hematopoiesis.

scholarly journals The interaction in vitro of Pneumocystis carinii with macrophages and L-cells.

1978 ◽  
Vol 147 (1) ◽  
pp. 157-170 ◽  
Author(s):  
H Masur ◽  
T C Jones
Keyword(s):  
Pneumocystis Carinii ◽  
Significant Degree ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
Humoral Factors ◽  
L Cells ◽  
Contrast Microscopy ◽  
Typical Morphology ◽  
Mouse Peritoneal Macrophages

A model was developed for studying the interaction between Pneumocystis, rat-derived cells, and humoral factors. Pneumocystis were obtained in large quantity by bronchial lavage of steroid-treated rats. The trophozoite was the predominant form obtained, and it could readily be recognized by phase contrast microscopy. Organisms maintained a typical morphology for at least 3 days in culture, and 10-20% took up radiolabeled nucleotides. Pneumocystis readily adhered to cell surfaces in a similar manner in alveolar macrophages from steroid-treated or normal rats, mouse peritoneal macrophages, and L-cells. Adherent organisms were not interiorized to a significant degree in the absence of antipneumocystis serum. After addition of rabbit antipneumocystis serum, rapid interiorization of organisms occurred from the surface of macrophages but not L-cells. Organisms appeared to be promptly destroyed within macrophages after interiorization. Persisting or multiplying intracellular forms were not seen. Antipneumocystis serum did not morphologically alter Pneumocystis. These observations suggest a role for antibody and mononuclear phagocytes during the immune response to Pneumocystis.

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