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At least 19 recordsLinked to original sources
PubMed1979

Sensitive and rapid method for determination of superoxide-generating activity of blood monocytes and its use as a probe for monocyte function in cancer patients.

The superoxide anion-generating capacity of human blood monocytes was measured by a sensitive and rapid method established by taking advantage of the fact that the generation of superoxide anions by monocytes was markedly enhanced by the combined stimulation of the cells with cytochalasin-E and wheat germ agglutinin. The activity was expressed by the initial rate of cytochrome c reduction after the addition of wheat germ agglutinin. The rate obtained with normal human monocytes was 0.73 +/- 0.19 nmol/min/10(5) monocytes (mean +/- SD, n = 10). Because of its sensitivity, the method required only 10(5) monocytes and can be used to follow the monocyte function in various patients. Preliminary data obtained with 15 cases of advanced cancer patients (0.29 +/- 0.10 nmol/min/10(5) monocytes) suggested a possible decrease of the superoxide-generating activity, at least in some state of cancer patients. It appears that measurement of superoxide-generating activity will be meaningful to monitor monocyte function.

Adult↗
PubMed1976

Tube leukocyte (monocyte) adherence inhibition assay for the detection of anti-tumour immunity. III. "Blockade" of monocyte reactivity by excess free antigen and immune complexes in advanced cancer patients.

Leukocytes from patients with limited cancer display LAI reactivity whereas leukocytes from patients with metastatic cancer frequently demonstrate no reactivity in the tube LAI assay. The leukocytes (monocytes) of reactive patients react with tumour antigen through specific cytophilic anti-tumour IgG antibody bound to the monocyte's Fc cell surface receptors. The non-reactive monocytes from patients with advanced cancer lacked the ability to bind free cytophilic anti-tumour antibody. Moreover, the serum of the non-reactive patient contained no free cytophilic anti-tumour antibody capable of "arming" normal leukocytes. The serum of patients with large tumour burdens contained free tumour antigenic determinants capable of absorbing free cytophilic anti-tumour antibody from the serum of reactive patients or when preincubated with reactive leukocytes abrogating their LAI responsiveness immunologically specifically. Blocking was immunologically specific; therefore, the specificity must reside in the tumour antigenic determinant since immune complexes are bound nonspecifically. The tumour antigen coat was removed by gentle trypsinization of the monocyte's surface. This restored the monocyte's capacity to react with the sensitizing tumour antigen and to bind free cytophilic antibody from the microenvironment. Nonreactivity in the tube LAI assay of patients with metastatic cancer was not the result of a numerical deficit of circulating monocytes but was mediated by an excess of tumour antigen in the microenvironment of the sensitized monocyte.

Adenocarcinoma↗
PubMed1978

Monocytes and macrophages in malignant melanoma. II. Lysis of antibody-coated human erythrocytes as an assay of monocyte function.

Peripheral blood mononuclear cells will lyse antibody-treated human erythrocytes. Using Group A red cells and a hyperimmune anti-A1 serum, we have devised a microassay for the cytolytic capacity of mononuclear cell suspensions. The effector cells responsible for red-cell lysis are mononuclear, adherent and phagocytic, and their activity is blocked by aggregated IgG. Their presence correlates well with non-specific esterase-containing cells and we conclude that they are monocytes. Dose-response curves of red-cell lysis plotted against numbers of monocytes were used to derive a simple parameter expressing the number of monocytes needed to lyse 15% of the 51Cr-labelled red cells. The assay was applied to a group of 27 normal controls and 36 patients with a histologically proven diagnosis of malignant melanoma. The results indicate that monocytes from patients show significantly greater lytic activity than those from the controls. These data suggest that monocytes from cancer patients are in some way activated, and that other defects in monocyte function which have been detected in cancer patients (defective chemotaxis and maturation) may be associated with monocyte "activation".

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Morphological and immunological similarity of the monocytes from pure and mixed monocytic leukaemias.

Morphological and immunological marker data on a patient with 'pure' monocytic leukaemia are presented and compared with those of 6 cases of clearly mixed myelomonocytic leukaemia with a variable monocytic component. In all patients studied, the leukaemic monocytes expressed a receptor for the Fc of IgG, and IgG sensitization markedly enhanced phagocytosis of ox erythrocytes. A variable, but lower, percentage of the leukaemic monocytes had a receptor for mouse C3, but the cells uniformly lacked surface immunoglobulin and receptors for the Fc of IgM and for unsensitised mouse erythrocytes. Cytochemical and ultrastructural study also showed no clear difference between the monocytes of the 'pure' and mixed monocytic leukaemias. This report therefore lends no support to the concept of distinct types of monocytic leukaemia.

Binding Sites, Antibody↗
PubMed1979

Functional characteristics of monocytes. II. Further observations on lymphocyte-monocyte collaboration in the response to phytomitogens.

Monocytes play a crucial role in the response of lymphocytes to phytomitogens. This role is evident during the very early events after exposure to the mitogen. Thus, significant lymphocyte transformation does occur when monocytes are removed from the culture within a few hours after exposure to mitogen, and the presence of monocytes after the initial period is no longer necessary. Monocytes appear to be required for the early increase in protein synthesis and burst in RNA synthesis following exposure to the mitogen. Monocytes may help in lymphocyte responses partly by longer range, by way of release of soluble humoral factors into culture supernatant fluids. Temperature dependence of the effect of pulse exposure of lymphocytes to these supernatants raises the possibility that membrane receptors on these cells to humoral factors released by monocytes may exist. Moncytes do not appear to act primarily by preserving the viability of lymphocytes in culture.

Cells, Cultured↗
PubMed1978

Antigens in human monocytes. III. Use of monocytes in typing for HLA-D related (DR) antigens.

Monocyte preparations were obtained from the peripheral blood by adherence to plastic dishes. The number of monocytes obtained was significantly greater than the number of B cells recovered from similar samples. Monocytes could be frozen and thawed with relatively little loss in cell numbers or viability. Cytotoxicity tests were performed most reliably at 20 degrees C. Under these conditions, autoantibodies were rare, and normal sera were consistently negative. Serologic reactions obtained with monocytes correlated well with the known specificities of the monocyte panel. Typing results in both normal and diseased populations were similar to results obtained with B lymphocytes. Moreover monocyte cytotoxicity tests were more convenient and easier to read than similar tests performed with B cells.

Arthritis, Rheumatoid↗
PubMed1979

Terminal Ph1-positive monocytic crisis in chronic myeloid leukemia providing evidence for the promyelocytic origin of monocytes.

A case of Ph1-positive chronic granulocytic leukemia in described in which a terminal monocytic crisis developed. The case still was Ph1-positive at the time of the monocyte crisis. Bone marrow smears contained promyelocytes and early granulocytes, but most of the cells belonged to the monocyte series as cytochemistry disclosed. No blast cells could be detected. Cytochemically, transitions between promyelocytes and promonocytes could be demonstrated. From these findings and those from the literature it is concluded that the monocytes of the terminal crisis in our case belonged to the leukemic cell strain and that these monocytes developed from non-specific promyelocytes like granulocytes. Our observation does not provide evidence for the existence of a separate monoblast which would implicate disparity of granulocytopoiesis and monocytopoiesis already at the level of undifferentiated blast cells. This, in turn, would be equal to a re-introduction of a modified polyphyletic theory of white blood cell formation.

Adult↗
PubMed1978

Serological characterization of human monocytes for HLA, B-lymphocyte, granulocyte, and monocyte-associated antigens by cytotoxicity testing.

Highly enriched preparations of monocytes, B and T lymphocytes, and granulocytes from 18 normal donors were serotyped in parallel in a complement-dependent cytotoxicity assay using allogeneic and heterologous antisera defining three independent tissue antigen systems. HLA and B-lymphocyte tissue antigens were detected on human monocytes although granulocyte antigens were absent. By cytotoxicity testing the presence of Ia-like antigens on monocytes was significantly diminished compared to the autologous B-lymphocyte population and has important implications in B-lymphocyte serology. The study indentified a number of human antisera obtained from multitransfused subjects and pre- and post-transplant organ recipients that were non-HLA and appeared to define monocyte-associated antigens. The serological implications of surface antigen expression on human monocytes compared with other peripheral blood cells are discussed.

B-Lymphocytes↗
PubMed1979

Long-term human peripheral blood monocyte cultures: establishment, metabolism and morphology of primary human monocyte-macrophage cell cultures.

Human peripheral blood monocytes were maintained in in vitro culture for periods up to 4 months using a non-human serum source. Monocytes were cultured in Dulbecco's modified Eagle's medium buffered with 20 mM HEPES and containing 10% horse serum and 10% foetal calf serum. The metabolic and morphological changes which occur in vitro were investigated using microtitre, Linbro and T 25 cultures. During culture, monocytes increased in size, had increased membrane activity as visualized by SEM, and differentiated into a morphologically heterogeneous population of fusiform and epithelioid shapes. These cell types retained the ability to phagocytose E glut and EA and to rosette with EA and EAC. Larger giant polynucleated cells were also observed during culture; many of these lacked the ability to bind or phagocytose inert or antibody-coated erythrocytes. Increases in lysozyme release and acid phosphatase activity also occurred during culture. Cultured monocytes exhibited characteristic profiles of leucine and uridine uptake with maximal activity observed by 5 days of culture. There was no detectable uptake of thymidine. Detailed analysis of regulatory processes involved in monocyte growth and differentiation could be performed with this in vitro system.

Cells, Cultured↗
PubMed1979

Humoral and formed elements of blood modulate the response of peripheral blood monocytes. I. Plasma and serum inhibit and platelets enhance monocyte adherence.

Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in vitro when they are suspended in Hanks' media. Increasing amounts of autologous serum or heat-inactivated plasma in the cell suspensions prevented the adherence of both monocytes and lymphocytes. The inhibitory effect of plasma was separated into three areas of activity by chromatography on Sephacryl S-200. The profile of inhibitory activity did not coincide with the protein elution profile, suggesting that inhibition was not a nonspecific protein effect. A layer of adherent platelets overcame the inhibitory effect of plasma on monocyte adherence. Platelets selectively increased monocyte as opposed to lymphocyte adherence and this was specific for platelets in that neither neutrophils nor fibroblasts could substitute for platelets. Both plasma and platelets acted directly on monocytes.

Animals↗
PubMed1979

Transformation of monocytes into amoeboid microglia in the corpus callosum of postnatal rats, as shown by labelling monocytes by carbon particles.

Two successive intravenous doses of carbon suspension were given at 24 hourly intervals into six days old rats. These animals were killed at intervals ranging from 1 to 9 days after the second injection. The corpus callosum and neighbouring structures were examined for cells containing ingested colloidal carbon particles in their cytoplasm. Twenty four hours after the second injection, a variable number of carbon-labelled monocytes were adherent to the luminal wall of blood vessels in the corpus callosum. Numerous carbon-labelled cells appeared to have left the lumen and entered the brain tissue surrounding the vessels. These perivascular carbon-labelled monocytes in the neuropil displayed a large pale nucleus with fine chromatin granules. The phagocytic amoeboid microglia in the corpus callosum were unlabelled at first, although a few cells of a similar nature in the cavum septi pellucidi did show carbon particles in their cytoplasm. Four or five days after the second carbon injection perivascular carbon-labelled monocytes were rare, but carbon particles were now present in the amoeboid microglia. At 8 days amoeboid microglia were virtually absent from the corpus callosum but carbon particles now appeared in cells which closely resembled microglia (flattened nucleus, coarse chromatin, scanty cytoplasm at one pole). The sequential appearance of carbon particles in monocytes, amoeboid microglia, and microglia, suggests that monocytes transform into microglia by way of an amoeboid microglial stage.

Aging↗
PubMed1978

Monocytes and macrophages in malignant melanoma. III. Reduction of nitroblue tetrazolium by peripheral blood monocytes.

Peripheral-blood monocytes from normal individuals and from patients with malignant melanoma reduce nitroblue tetrazolium (NBT). A quantitative assay for dye reduction was applied to 25 healthy donors and 31 patients with malignant melanoma. NBT reduction expressed as dye reduction per monocyte was significantly impaired in patients with disseminated disease, and they responded poorly to a phagocytic stimulus. Monocytes from patients with micrometastatic disease, however, showed normal resting NBT reduction but, following exposure to a suspension of latex-polystyrene, showed significantly greater NBT reduction than those from normal individuals. Since NBT reduction is an indirect measure of intracellular hexose-monophosphate-shunt activity we conclude that the monocytes from patients with minimal disease are in some way activated.

Adolescent↗
PubMed1979

Monocytes and macrophages in malignant melanoma IV. Effects of C. parvum on monocyte function.

Assays for the capacity of peripheral-blood monocytes (a) to mature in vitro into macrophages, (b) to reduce nitro-blue tetrazolium (NBT) and (c) to lyse antibody-coated human Group A red cells, were applied to a group of 82 patients with histologically proven malignant melanoma. In patients with micrometastatic disease there was an enhancement of red-cell lysis and NBT reduction, suggesting that their monocytes are in some way "activated", whereas NBT reduction was suppressed in those with overt dissemination. Monocyte maturation in vitro was impaired in all patient groups to an extent which correlated with overall tumour burden. Corynebacterium parvum was administered i.v. to 12 patients with disseminated disease and by the intradermal route to 24 patients with micrometastatic disease. The 3 monocyte functions were significantly enhanced by C. parvum.

Bacterial Vaccines↗
PubMed2026

Monocytes Defined by Platelet Interactions and Oxidative Stress Signaling Underlie HIV-Associated Atherosclerosis.

BACKGROUND: Monocytes contribute to atherosclerosis by migrating into inflamed endothelium and differentiating into lipid-laden macrophages. In people living with HIV, chronic inflammation increases atherosclerosis risk, yet the role of specific monocyte subsets remains unclear. We investigated how distinct monocyte populations contribute to vascular pathology in early HIV-associated atherosclerosis. METHODS: We profiled 123 965 circulating monocytes using single-cell RNA sequencing and integrated plasma microparticle proteomics in 32 individuals stratified by HIV and atherosclerosis status. Supervised learning identified cluster- and disease-specific signatures, validated by platelet-monocyte cocultures, reverse transcription-quantitative polymerase chain reaction, bulk RNA sequencing, flow cytometry, and ELISA. RESULTS: Seven monocyte clusters were identified, including a subset characterized by platelet-monocyte complexes. Bulk RNA sequencing of platelet-monocyte cocultures revealed platelet-driven upregulation of genes involved in inflammation, lipid metabolism, oxidative stress, and endothelial adhesion. Platelet-monocyte complex-derived macrophages secreted higher levels of TGF-β (transforming growth factor-β) and IL-10 (interleukin-10), displayed decreased CD14 and increased CD80/CD86 while retaining CD36, and promoted endothelial-to-mesenchymal transition (decreased expression of CDH5 and PECAM1; increased expression of S100A4 and markers of vascular inflammation (ICAM1), VCAM), and IL-6 (interleukin-6), and CCL2 (C-C motif chemokine ligand 2) secretion). Additionally, CD14+ monocytes from HIV+ atherosclerosis-negative and HIV+ atherosclerosis-positive groups showed enhanced ROS-NRF2 (reactive oxygen species-nuclear factor erythroid 2-related factor 2) pathway activities, supported by increased basal and H2O2-induced p90RSK phosphorylation, indicating oxidative stress priming. CONCLUSIONS: Two monocyte clusters contribute independently to vascular immune dysregulation in people living with HIV. Platelet-monocyte complex-derived macrophages promote endothelial dysfunction while adopting a profibrotic cytokine profile. CD14+ monocytes show heightened oxidative signaling and stress responses, consistent with vascular activation. Together, these mechanisms may accelerate atherosclerosis development in HIV, even in the absence of traditional cardiovascular risk factors.

Humans↗
PubMed1979

The role of monocytes in human lymphocyte activation by mitogens.

Studies were performed to determine the role of monocytes in human lymphocyte activation by mitogens. Velocity sedimentation at 1 x G in a new apparatus was utilized to obtain highly purified lymphocyte fractions (LF) nearly free of monocytes (0.02 to 0.4%) and a fraction (MF) enriched for monocytes (64 to 92%). The average peak responses of the lymphocyte fractions to phytohemagglutinin, concanavalin A, and pokeweed mitogen were 19, 10, and 9% of the responses achieved with unfractionated lymphocyte cultures containing approximately 20% monocytes. These changes were not attributable to altered dose requirements. When mitomycin-C-treated MF cells were used to reconstitute LF cultures, it was found that 4% monocytes fully restored the response to phytohemagglutinin whereas 8 to 16% monocytes were required for a normal response to the other mitogens. Higher numbers of MF cells produced supranormal responses, with 35 to 50% monocytes resulting in the optimal stimulation. Allogeneic monocytes were able to fully reconstitute the response of LF, and 2-mercaptoethanol (50 microM) was only slightly effective. In exploring possible mechanisms by which monocytes potentiate the mitogenic activity of lymphocytes, it was found that the supernatants of MF cultures could partially, but not completely, reconstitute LF responses, suggesting that contact with MF may be required for optimal effectiveness. Addition of graded numbers of monocytes to LF altered both the kinetics of the response and the peak level of proliferation. Monocyte depletion also resulted in markedly decreased survival of cultured unstimulated LF. These observations suggest a variety of possible effects of monocytes in potentiating mitogenic responses, including contact-mediated interactions with lymphocytes (possibly to present the mitogen optimally); enhancement of proliferation kinetics and the size of the responding subpopulation, and maintenance of a requisite growth factor(s) in the culture. Small differences in the monocyte content of cultured lymphocyte preparations may thus account for many of the often observed variations in mitogen responsiveness.

Cell Survival↗
PubMed2026

Translating single-cell RNA sequencing into monocyte direct leukocyte subpopulation-transcript abundance assay ratio-based biomarkers (IFI27/PSAP or IFI27/CTSS) for clinical detection of viral infection.

A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.

Humans↗