scholarly journals Subretinal mononuclear phagocytes induce cone segment loss via IL-1β

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chiara M Eandi ◽  
Hugo Charles Messance ◽  
Sébastien Augustin ◽  
Elisa Dominguez ◽  
Sophie Lavalette ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Transitional Zone ◽  
Mononuclear Phagocyte ◽  
Geographic Atrophy ◽  
Mononuclear Phagocytes ◽  
High Acuity ◽  
Human And Mouse

Photo-transduction in cone segments (CS) is crucial for high acuity daytime vision. For ill-defined reasons, CS degenerate in retinitis pigmentosa (RP) and in the transitional zone (TZ) of atrophic zones (AZ), which characterize geographic atrophy (GA). Our experiments confirm the loss of cone segments (CS) in the TZ of patients with GA and show their association with subretinal CD14+mononuclear phagocyte (MP) infiltration that is also reported in RP. Using human and mouse MPs in vitro and inflammation-prone Cx3cr1GFP/GFP mice in vivo, we demonstrate that MP-derived IL-1β leads to severe CS degeneration. Our results strongly suggest that subretinal MP accumulation participates in the observed pathological photoreceptor changes in these diseases. Inhibiting subretinal MP accumulation or Il-1β might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.

scholarly journals Increased in vitro and in vivo generation of procoagulant activity (tissue factor) by mononuclear phagocytes after intralipid infusion in rabbits

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1391-1395 ◽  
Author(s):  
P Montemurro ◽  
A Lattanzio ◽  
G Chetta ◽  
L Lupo ◽  
L Caputi-Iambrenghi ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Procoagulant Activity ◽  
Sterile Saline ◽  
Functional Changes ◽  
Before And After

Abstract Intralipid, a fat emulsion widely used in parenteral nutrition, can produce marked functional changes of the mononuclear phagocyte system. We investigated the effect of Intralipid administration on the generation of procoagulant activity by rabbit mononuclear phagocytes. Two groups of ten rabbits given either a single infusion of Intralipid 10% or a similar volume of sterile saline were studied before and after infusion. Procoagulant activity was measured on isolated blood mononuclear cells after incubation with and without endotoxin, using a one-stage clotting assay. Cells from animals infused with Intralipid produced significantly more procoagulant activity than controls (P less than .01). Results were similar when freshly collected whole blood was incubated with and without endotoxin, and procoagulant activity was measured on subsequently isolated mononuclear cells (P less than .01). In addition, when rabbits were given a single injection of endotoxin, blood and spleen mononuclear cells harvested 50 to 60 minutes after the injection from animals pretreated with Intralipid expressed five to seven times more procoagulant activity than did cells from animals pretreated with saline. In all instances, procoagulant activity was identified as tissue factor. These findings suggest that Intralipid may cause functional changes in mononuclear phagocytes, resulting in increased production of tissue factor on incubation in short-term culture in vitro and in response to endotoxin in vivo.

scholarly journals Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 994-999 ◽  
Author(s):  
P LeMarbre ◽  
JJ Rinehart ◽  
NE Kay ◽  
R Vesella ◽  
HS Jacob
Keyword(s):  
Tumor Cell ◽  
Metabolic Activation ◽  
Human Monocyte ◽  
Cell Interaction ◽  
Competitive Inhibitor ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Tumoricidal Activity

The mononuclear phagocyte is well established as an in vitro cytotoxic effector cell for certain human tumors. The mechanism(s) for this action remains unclear. Increased levels of lysozyme, a cationic enzyme synthesized in large amounts by mononuclear phagocytes, are associated with increased resistance to transplantable animal tumors. In this study, we provide evidence that human lysozyme, isolated from the urine of leukemic patients, has marked potentiating effects on human monocyte- tumor-cell cytocidal activity. In addition, lysozyme-exposed monocytes incorporate increased quantities of leucine, suggesting that monocytes are capable of amplifying their own metabolic activation by secreting an endogenous constituent. Tri-N-acetyl-glucosamine, a competitive inhibitor for the active site of lysozyme, inhibits cytocidal activity. Conversely, protamine, an extraneous albeit similarly positively charged molecule, increases monocyte-mediated tumor cytotoxicity; this protamine effect is negated by heparin. We conclude that lysozyme, at least partially by its positive charge, is capable of enhancing in vitro monocyte tumor cell cytotoxicity; its in vivo secretion may potentiate monocyte-tumor-cell interaction.

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 Leishmania mexicana amazonensis: heterogeneity in 5-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection

1988 ◽  
Vol 83 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Suzana Côrte-Real ◽  
Gabriel Grimaldi Junior ◽  
Maria de Nazareth Leal de Meirelles
Keyword(s):  
Enzyme Activity ◽  
Peroxidase Activity ◽  
Activity Analysis ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Leishmania Mexicana ◽  
Cytoplasmic Vesicles ◽  
Murine Cutaneous Leishmaniasis

The degree of maturation of cells of the Mononuclear Phagocyte System (MPS), during in vivo and in vitro infection by Leishmania mexicana amazonenesis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastrctural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells, and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. only a few mcrophages, demonstrating 5'-nucleotidase positive reaction in both the plasma membrane and within their cytoplasmic vesicles, were found scattered in the chronic inflammation at the L. m. amazonensis lesions in albino mice. However, by the peroxidase activity analysis, we were also able to demonstrate the presence of immature MPS cells, which predominate, together with parasitized vacuolated macrophages, in chronic lesions induced in this systemby L. m. amazonensis. The implications of these results on the pathogenesis of murine cutaneous leishmaniasis are discussed.

The Milk Mononuclear Phagocyte

PEDIATRICS ◽  
1979 ◽  
Vol 64 (5) ◽  
pp. 745-749
Author(s):  
Jane Pitt
Keyword(s):  
Protein Synthesis ◽  
Smooth Endoplasmic Reticulum ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Human Colostrum ◽  
The One ◽  
Inhibitor Of Protein Synthesis ◽  
Glass Surfaces

A large number of mononuclear phagocytes are present in human colostrum and milk and are transferred from mother to baby. Although one can only speculate on their role in vivo, there is a modest amount of information about their characteristics in vitro which will be reviewed in this paper. About 80% of the one to two million leukocytes in colostrum and early human milk are mononuclear phagocytes1,2 as determined by esterase staining,3 latex ingestion, and glass adherence. While See Table in the PDF Document their concentration diminishes with longer lactation, the number of macrophages secreted daily is large (Table 1). The milk mononuclear phagocyte spreads avidly onto glass surfaces extending long filamentous processes into the environment (Fig 1). Trypan blue is rapidly taken up into the lysozomes of living cells (Fig 2) as is acridine orange. These cells are lipid laden (Fig 3) and on ultrastructural analysis one sees that the lipid inclusions are not always membrane bound (Fig 4). Mitochondria, an indication of oxidative metabolism, and rough and smooth endoplasmic reticulum, suggesting active protein synthesis, are plentiful. Comparisons between milk and blood mononuclear phagocytes are listed in Table 2. Lysozyme is one of the proteins synthesized and secreted by the milk mononuclear phagocyte. By competitive binding, radioimmunoassay milk macrophages can be shown to release 100 ± 8 ng lysozyme/ 5 x 105 cells into the supernatant; the level is reduced to 20 ± 4 ng when these cells are cultured in the presence of 10 µg/ml of cyclohexamide, an inhibitor of protein synthesis. Moreover, it appears that these cells make C3 and C4.

Human monocytes lose 5-lipoxygenase and FLAP as they mature into monocyte-derived macrophages in vitro

1996 ◽  
Vol 271 (1) ◽  
pp. C372-C377 ◽  
Author(s):  
W. L. Ring ◽  
C. A. Riddick ◽  
J. R. Baker ◽  
D. A. Munafo ◽  
T. D. Bigby
Keyword(s):  
Northern Blot Analysis ◽  
Mononuclear Phagocyte ◽  
Lipoxygenase Activity ◽  
Mononuclear Phagocytes ◽  
Macrophage Phenotype ◽  
Lipoxygenase Pathway ◽  
Maturation In Vitro ◽  
Enhanced Expression

Previous studies in mononuclear phagocytes have shown that macrophages have substantially greater 5-lipoxygenase activity than monocytes and that this is associated with greater amounts of 5-lipoxygenase and its activating protein (FLAP). The aim of this study was to examine the effect of mononuclear phagocyte maturation in vitro on 5-lipoxygenase expression. At baseline, monocytes had significant 5-lipoxygenase activity, but then lost all detectable 5-lipoxygenase activity over 7 days. Immunoblot and Northern blot analysis revealed that immunoreactive protein and mRNA for both 5-lipoxygenase and FLAP were significantly decreased over time. These studies demonstrate that in vitro differentiation of monocytes into a macrophage phenotype is not accompanied by the enhanced expression of 5-lipoxygenase and FLAP seen in macrophages derived from in vivo sources. In fact, baseline expression of 5-lipoxygenase and FLAP by monocytes is lost in vitro. These studies have clear implications for the use of cultured monocytes as a model of macrophages, and they also further our understanding of the regulation of the 5-lipoxygenase pathway.

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 Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 994-999 ◽  
Author(s):  
P LeMarbre ◽  
JJ Rinehart ◽  
NE Kay ◽  
R Vesella ◽  
HS Jacob
Keyword(s):  
Tumor Cell ◽  
Metabolic Activation ◽  
Human Monocyte ◽  
Cell Interaction ◽  
Competitive Inhibitor ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Tumoricidal Activity

Abstract The mononuclear phagocyte is well established as an in vitro cytotoxic effector cell for certain human tumors. The mechanism(s) for this action remains unclear. Increased levels of lysozyme, a cationic enzyme synthesized in large amounts by mononuclear phagocytes, are associated with increased resistance to transplantable animal tumors. In this study, we provide evidence that human lysozyme, isolated from the urine of leukemic patients, has marked potentiating effects on human monocyte- tumor-cell cytocidal activity. In addition, lysozyme-exposed monocytes incorporate increased quantities of leucine, suggesting that monocytes are capable of amplifying their own metabolic activation by secreting an endogenous constituent. Tri-N-acetyl-glucosamine, a competitive inhibitor for the active site of lysozyme, inhibits cytocidal activity. Conversely, protamine, an extraneous albeit similarly positively charged molecule, increases monocyte-mediated tumor cytotoxicity; this protamine effect is negated by heparin. We conclude that lysozyme, at least partially by its positive charge, is capable of enhancing in vitro monocyte tumor cell cytotoxicity; its in vivo secretion may potentiate monocyte-tumor-cell interaction.

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