Parameters affecting the in vitro maturation of human monocytes to macrophages

Maoz, Helen; Polliack, Aaron; Barak, Vivian; Yatziv, S; Biran, S; Giloh, Haim; Treves, Abraham J.

doi:10.1002/stem.5530040303

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…Monocytes are initially activated by their adherence to a solid substrate; however, many of the activation parameters return to their basal levels after 24 h of culture (14,21,22,36,45,49). Adherence and spreading of monocytes to culture dishes induce spontaneous differentiation to macrophages, which involves a number of physical and biochemical changes of the cells (11,30). The characteristic morphological changes generally observed during conversion of a monocyte to a macrophage include an increase in cell size, as well as development of a higher cytoplasm-to-nucleus ratio (24).…”

Section: Discussionmentioning

confidence: 99%

Degradation ofChlamydia pneumoniaeby Peripheral Blood Monocytic Cells

Wolf¹,

Fischer²,

Hackstadt³

2005

Infect Immun

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Chlamydia pneumoniae is a common human respiratory pathogen that has been associated with a variety of chronic diseases, including atherosclerosis. The role of this organism in the pathogenesis of atherosclerosis remains unknown. A key question is how C. pneumoniae is transferred from the site of primary infection to a developing atherosclerotic plaque. It has been suggested that circulating monocytes could be vehicles for dissemination of C. pneumoniae since the organism has been detected in peripheral blood monocytic cells (PBMCs). In this study we focused on survival of C. pneumoniae within PBMCs isolated from the blood of healthy human donors. We found that C. pneumoniae does not grow and multiply in cultured primary monocytes. In C. pneumoniae-infected monocyte-derived macrophages, growth of the organism was very limited, and the majority of the bacteria were eradicated. We also found that the destruction of C. pneumoniae within infected macrophages resulted in a gradual diminution of chlamydial antigens, although some of these antigens could be detected for days after the initial infection. The detected antigens present in infected monocytes and monocyte-derived macrophages represented neither chlamydial inclusions nor intact organisms. The use of {N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]}-6-aminocaproyl-D-erythro-sphingosine as a vital stain for chlamydiae proved to be a sensitive method for identifying rare C. pneumoniae inclusions and was useful in the detection of even aberrant developmental forms.

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Section: Discussionmentioning

confidence: 99%

Degradation ofChlamydia pneumoniaeby Peripheral Blood Monocytic Cells

Wolf¹,

Fischer²,

Hackstadt³

2005

Infect Immun

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“…Serum may impact on macrophage physiology such as the expression ofcertain markers of maturation (8,9). To determine if iron regulation is altered under serumless conditions, we assessed intracellular ferritin content and transferrin receptor expression on IFN'y-activated monocytes cultured in the absence of serum.…”

Section: Methodsmentioning

confidence: 99%

Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma.

Byrd

Horwitz²

1993

J. Clin. Invest.

139

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We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFNy and iron transferrin. In a previous study, we demonstrated that IFN-y downregulates the expression on human monocytes of transferrin receptors, the major source of iron for the cell. In the present study, we show that IFNy also downregulates the intracellular concentration of ferritin, the major iron storage protein in the cell. By radioimmunoassay, the mean ferritin content of nonactivated monocytes was 361±107 fg/monocyte (mean±SEM) whereas the mean ferritin content of IFNy-activated monocytes was 64±13 fg/monocyte, an 82% reduction with activation (P < 0.01, t test). Consistent with its downregulating effect on these iron proteins, IFNy treatment also results in decreased iron incorporation. IFNy-activated monocytes incorporated 33% less iron from 59Fe-transferrin than nonactivated monocytes (P < 0.05, t test). Gel filtration chromatography revealed that incorporated iron is located primarily in ferritin in both nonactivated and IFN-y-activated monocytes. Ferritin in IFN'yactivated monocytes is saturated with approximately three times as much 59Fe as ferritin in nonactivated monocytes.We have also explored the effect of iron transferrin on transferrin receptor expression and intracellular ferritin content in human monocytes. We have found that iron transferrin markedly upregulates both transferrin receptor expression and intracellular ferritin content in both nonactivated (2.3-and 1.3-fold, respectively) and IFN'y-activated (3.4-and 2.9-fold, respectively) monocytes.This study demonstrates that transferrin receptor expression and intracellular ferritin content in human monocytes is unidirectionally and coordinately upregulated by iron transferrin and unidirectionally and coordinately downregulated by IFN-y. (J. Clin. Invest. 1993. 91:969-976.)

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“…Both intracellular and secreted de n o w synthesized azM (immunoprecipitated from equivalent total trichloroacetic-acid-precipitable proteins) is shown to be drastically decreased in lipopolysaccharide-treatred cells as compared to macrophages after unimpaired in vitro differentation. In contrast, long-term incubation with the synthetic glucocorticoid dexamethasone did not influence azM synthesis, although dexamethasone has been previously reported to inhibit monocyte -macrophage maturation [51] (these authors could have had endotoxin contaminations in their dexamethasone solutions).…”

Section: Resultsmentioning

confidence: 66%

Repression of alpha2-macroglobulin and stimulation of alpha1-proteinase inhibitor synthesis in human mononuclear phagocytes by endotoxin

Ganter¹,

Bauer²,

SCHULZ-HUOTARI³

et al. 1987

Eur J Biochem

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Mononuclear phagocytes are a bone-marrow-derived subgroup of white blood cells which circulate as monocytes and, after differentiation into macrophages, become resident in many tissues. By synthesizing the important proteinase inhibitors a,-macroglobulin and al-proteinase inhibitor mononuclear phagocytes contribute to the control of proteolysis both in blood and tissues. Applying a culture system which enables human blood monocytes to differentiate into macrophages in vitro, synthesis of a,-macroglobulin and al-proteinase inhibitor was studied. The normal course of monocyte -macrophage maturation is accompanied by a strong increase of specific a,-macroglobulin synthesis and a concomitant slight decrease of al-proteinase inhibitor. a,-Macroglobulin can be designated as a marker protein of the monocyte/macrophage differentiation. Endotoxin (Salmonella ryphi) in a concentration as low as 100 ng/ml strongly represses a,-macroglobulin synthesis both in monocytes and macrophages. Furthermore, endotoxin completely abolishes the induction of a,-macroglobulin synthesis during the course of normal monocyte in vitro cultivation, indicating that endotoxin is a strong inhibitor of the monocyte -macrophage maturation. In contrast to a,-macroglobulin, al-proteinase inhibitor synthesis is strongly stimulated by endotoxin in monocytes as well as in macrophages.The cells of the mononuclear phagocyte system derive from stem cells in the bone marrow, linking monoblasts, promonocytes, monocytes and the heterogeneous tissue macrophages (for review see [l -31). Cells of this lineage develop over several days in the marrow and circulate as monocytes in the peripheral blood for a few further days before migrating into different tissues, where they remain resident for up to several months as macrophages. Macrophages are present in the liver (as Kupffer cells), lung (as alveolar macrophages), bone (as osteoclasts) and several other tissues. The development of the blood monocytes into macrophages is accompanied by marked morphological and biochemical changes and is designated as terminal maturation. Differentiation of monocytes into macrophages can be studied in vitro by cultivation of purified populations of human peripheral blood monocytes within hydrophobic Teflon foils in the presence of human serum [4]. In vitro maturation closely resembles differentiation in vivo [5].Secretory products of mononuclear phagocytes are involved in several macrophage functions, such as immunoregulation and the killing of bacteria (for review see [3,61). Several proteinase inhibitors were found to belong to the proteins secreted by mononuclear phagocytes including azCorrespondence to J. Bauer, Medizinische Universitatsklinik, Hugstetter StraSe 55, D-7800 Freiburg, Federal Republic of Germany This work is dedicated to Prof. Dr Georg Wilhelm Lohr on the occasion of his 65th birthday.Abbreviations. E~M , a2-macroglobulin, q P I , ccl-proteinase inhibitor; RPMI, Roswell Park Memorial Institute 1640 medium. macroglobulin (azM) [7] and a]-proteinase inhibitor (a...

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Parameters affecting the in vitro maturation of human monocytes to macrophages

Cited by 13 publications

References 26 publications

Degradation ofChlamydia pneumoniaeby Peripheral Blood Monocytic Cells

Degradation ofChlamydia pneumoniaeby Peripheral Blood Monocytic Cells

Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma.

Repression of alpha2-macroglobulin and stimulation of alpha1-proteinase inhibitor synthesis in human mononuclear phagocytes by endotoxin

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