SEARCH · PubMed Health

Results for “classical monocytes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed1987

Stimulation of prostaglandin E2 and thromboxane B2 production by human monocytes in response to interleukin-2.

Interleukin 2 (IL-2) is a potent lymphokine involved in the regulation of immune responses and is classically regarded as a stimulus for the activation and growth of T-cells. Recent reports have demonstrated the IL-2 dependent activation of human peripheral blood lymphocytes into lymphokine activated killer cells capable of lysing tumor cells both in vitro and in vivo. In this study we report data which clearly show IL-2 may also act to down-regulate the immune response by inducing the synthesis of arachidonic acid metabolites with known immunosuppressive actions. Stimulation of peripheral human blood monocytes with IL-2 caused an increased production of prostaglandin E2 (PGE2) and thromboxane (TXB2) in a dose-dependent manner. Kinetic analysis showed no increase above controls after 6 hours and maximal levels by 10 hours; elevated levels were maintained after 45 hours of incubation. After 20 hours of stimulation with 2000 U/ml IL-2, the level of PGE2 and TXB2 were greater than three-fold above controls, 0.7 and 19 ng/10(6) cells, respectively. The stimulation was relatively specific in that neither prostacyclin nor leukotrienes were produced in response to IL-2. These data demonstrate that IL-2 acts on human monocytes to induce the secretion of PGE2 and TXB2.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Novel role of lipoxygenases in the inflammatory response: promotion of TNF mRNA decay by 15-hydroperoxyeicosatetraenoic acid in a monocytic cell line.

The metabolism of arachidonic acid via the lipoxygenase and cyclooxygenase pathways generates metabolites that regulate the inflammatory response. Although products of lipoxygenase are classically proinflammatory, recently it has been demonstrated that lipoxins, 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid exhibit anti-inflammatory activity. We now demonstrate for the first time that 15-HPETE regulates the production of the proinflammatory cytokine TNF posttranscriptionally by promoting degradation of LPS-induced TNFmRNA in a human monocytic cell line, Mono Mac 6. 15-HPETE causes a significant increase in the rate of TNF but not G3PDHmRNA degradation in the presence of the transcription inhibitor, actinomycin D. The decay of TNFmRNA is accelerated 1.7-fold, and its half-life is decreased by 57%. In view of its chemical and physical properties, we propose that 15-HPETE may function by destabilizing TNFmRNA by interaction with a trans-activating protein bound to the AU-rich element of TNFmRNA.

Arachidonic Acid↗

PubMed2003

The isoprostane 8-iso-PGE2 stimulates endothelial cells to bind monocytes via cyclic AMP- and p38 MAP kinase-dependent signaling pathways.

Increased levels of isoprostanes have been detected in human atherosclerotic lesions. To examine a possible role for 8-iso-prostaglandin E(2) (8-iso-PGE(2)) in atherogenesis, we tested the effect of 8-iso-PGE(2) on adhesion of leukocytes to human umbilical vein endothelial cells (EC). We demonstrate that 8-iso-PGE(2) stimulates EC to bind monocytes, but not neutrophils. This effect was inhibited by the thromboxane A(2) receptor antagonist SQ29548. Moreover, 8-iso-PGE(2) increased levels of cyclic AMP in EC, and monocyte adhesion induced by 8-iso-PGE(2) was blocked by a protein kinase A inhibitor, H89. In addition, 8-iso-PGE(2 )induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein (MAP) kinase and stimulated expression of EGR-1. A specific inhibitor of p38 MAP kinase (SB203580) abrogated monocyte binding, whereas an inhibitor of the ERK pathway (PD98059) did not block monocyte adhesion induced by 8-iso-PGE(2). Activation of nuclear factor-kappaB (NF-kappaB) and expression of NFkappaB-dependent genes intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin were not induced by 8-iso-PGE(2). Taken together, these results demonstrate that 8-iso-PGE(2) stimulates EC to specifically bind monocytes, but not neutrophils. This effect is mediated by cyclic AMP/protein kinase A- and p38 MAP kinase-dependent pathways and is independent of the classical inflammatory NFkappaB pathway. Thus, formation of 8-iso-PGE(2) may play an important role in chronic inflammatory diseases such as atherosclerosis by increasing adhesion and extravasation of monocytes.

Arteriosclerosis↗

PubMed1993

Binding, internalization, and degradation of mannose-terminated glucocerebrosidase by macrophages.

Mannose-terminated glucocerebrosidase (alglucerase; Ceredase) was designed for enzyme replacement therapy in Gaucher disease to take advantage of mannose receptor-mediated endocytosis by macrophages. To provide a rational basis for designing enzyme replacement therapy protocols, we examined the in vitro binding, uptake, and degradation of alglucerase by murine and human macrophages. Both were found to have approximately 500,000 mannose-dependent receptors for alglucerase per cell with a Kd of 10(-7) M at 0 degrees C. In contrast, the number of binding sites for mannose-bovine serum albumin (mannose-BSA), the classical ligand for the mannose receptor, was only approximately 20,000 with a Kd of 10(-8) M. Alglucerase was also bound in a mannose-dependent manner by cells that lack the capacity to bind mannose-BSA, such as Cos-1 cells, endothelial cells, and peripheral blood monocytes. The fact that the binding of alglucerase by macrophages was mediated principally by a receptor distinct from the classical mannose receptor that binds mannose-BSA was confirmed by differential inhibitors, viz., alpha-methyl-glucoside, fucose, and mannose-BSA, and by its independence on Ca2+. Uptake of alglucerase by macrophages at 37 degrees C was concentration dependent and half maximal at 10(-6) M. However, at a concentration of 10(-7) M, only 0.5% of the added alglucerase was incorporated into macrophages and approximately 50% of the alglucerase taken up was quickly released into the medium. Endothelial cells also manifest mannose-dependent binding and uptake of alglucerase and may therefore account for a large proportion of the infused alglucerase. Our data suggest that only a small amount of the alglucerase administered is effectively delivered to macrophages and that a more efficiently targeted enzyme might have a marked therapeutic advantage over mannose-terminated glucocerebrosidase.

Animals↗

PubMed1991

Complement C4-derived monocyte-directed chemotaxis-inhibitory factor. A molecular mechanism to cause polymorphonuclear leukocyte-predominant infiltration in rheumatoid arthritis synovial cavities.

To reveal the mechanism of the lesser infiltration of monocytes in synovial cavities with rheumatoid arthritis despite the presence of chronic inflammation, the synovial fluid from 15 rheumatoid arthritis patients was analyzed with respect to leukocyte chemotaxis. The synovial fluid possessed strong chemotactic activity to polymorphonuclear leukocytes but rather suppressed one to monocytes. The synovial fluid contained two different inhibitory activities in monocyte chemotaxis. One, which also suppressed polymorphonuclear leukocyte chemotaxis, was identified as alpha 1 protease inhibitor. The other, with molecular weight of 8 kd, possessed the specificity to monocytes and shared the antigenicity with complement C4 but not with C3 or C5. A similar inhibitor was generated in normal human plasma when the classical pathway of the complement system was initiated with aggregated human IgG, while it was not when alternative pathway was initiated with zymosan. The small size factor in the synovial fluid, apparently derived from C4, seemed to be a cyto-directed factor that might block an early part of signal transduction system of monocytes in the chemotaxis. After removal of the small-size inhibitor, the synovial fluid exhibited chemotactic ability to monocytes. Therefore the apparent C4-derived factor might play a key role in the polymorphonuclear leukocyte-predominant infiltration in the synovial fluid of rheumatoid arthritis.

Adult↗

PubMed2006

Vitamin D and cancer.

1,25-dihydroxy Vitamin D [1,25-(OH)(2)D] exerts its effects via the vitamin D receptor (VDR) that belongs to the steroid/thyroid hormone receptor superfamily leading to gene regulation which results in various biological responses. Within the last two decades, the receptor has been shown to be present not only in classical target tissues such as bone, kidney and intestine but also in many other non-classical tissues. Besides the almost universal presence of VDRs, some cell types (e.g. keratinocytes, monocytes, bone, placenta) are capable of metabolizing 25-hydroxyvitamin D to 1,25(OH)(2)D by the enzyme 1alpha-hydroxylase (CYP27B1). The combined presence of 25(OH)D-1alpha-hydroxylase as well as the specific receptor in several tissues introduced the idea of a paracrine role for 1,25(OH)(2)D. Moreover, it has been demonstrated that 1,25(OH)(2)D can induce differentiation and inhibit proliferation of a wide variety of cell types. The molecular mechanisms behind this antiproliferative action is thoroughly explored but the whole picture is still difficult to understand. Important cell cycle regulators are involved such as cyclins, cyclin dependent kinases and their corresponding inhibitors as well as E2F transcription factors and accompanying pocket proteins. However the precise hierarchical structure of this wide diversity of actions of 1,25(OH)(2)D on genes influencing cell cycle progression is not firmly established nor do we understand which pathways are essential and which redundant. The antiproliferative action makes 1,25-(OH)(2)D and its analogs a possible therapeutic tool to treat hyperproliferative disorders, among which different types of cancer. This review focuses on the effects of 1,25(OH)(2)D and its analogs on cell proliferation, the results in in vivo experiments in Vitamin D deficient or resistant animals to cancer and the current epidemiological and intervention studies linking Vitamin D status or treatment and human cancer.

Animals↗

PubMed2004

[Physiopathology of inflammatory events in asthma].

Inflammatory events in asthma include an initiation step dependent on dendritic cells, an effector step which involves the release of a large number of mediators by inflammatory cells, mastocytes, polymorphonuclear neutrophils and eosinophils, alveolar macrophages and monocytes, and lymphocytes; and a repair phase leading to airway remodeling. In addition to classic mediators such as histamine and leucotrienes, it is currently accepted that cytokines and chimokines play an essential role in local cellular trafficking. The bronchial endothelium and epithelium are simultaneously activated. Bronchial inflammation is constant in patients with allergic asthma and persists even in the absence of symptoms. Links between the intensity of the inflammatory response and the occurrence of airway remodeling suggest that therapeutic interventions should take place as early as possible, particularly in children.

Asthma↗

PubMed2003

Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor.

Leukocyte immunoglobulin-like receptor 1 (LIR-1), an inhibitory receptor expressed on monocytes, dendritic cells and lymphocytes, regulates cellular function by binding a broad range of classical and nonclassical major histocompatibility complex (MHC) class I molecules, and the human cytomegalovirus MHC class I homolog UL18. Here we describe the 3.4-A crystal structure of a complex between the LIR-1 D1D2 domains and the MHC class I molecule HLA-A2. LIR-1 contacts the mostly conserved beta(2)-microglobulin and alpha3 domains of HLA-A2. The LIR-1 binding site comprises residues at the interdomain hinge, and a patch at the D1 tip. The structure shows how LIR-1 recognizes UL18 and diverse MHC class I molecules, and indicates that a similar mode of MHC class I recognition is used by other LIR family members.

Amino Acid Sequence↗

PubMed2005

C-reactive protein does not opsonize early apoptotic human neutrophils, but binds only membrane-permeable late apoptotic cells and has no effect on their phagocytosis by macrophages.

BACKGROUND: It has been reported that C-reactive protein (CRP) binds both leukocyte FcgammaRIIA (CD32) and the plasma membrane of apoptotic cells. Since FcgammaRIIA becomes functionally enabled during neutrophil apoptosis, we sought to determine whether CRP bound to apoptotic neutrophils via FcgammaRIIA. METHODS: We prepared directly labelled CRP and demonstrated that it was essentially free of IgG. We looked for evidence of CRP binding to intact, membrane impermeable apoptotic human neutrophils and to FcgammaRIIA-transfected Jurkat cells. We examined the functional consequences of incubation with CRP upon phagocytosis of apoptotic cells by human monocyte-derived macrophages. RESULTS: We could not detect binding of purified soluble CRP to classical early apoptotic human neutrophils or to FcgammaRIIA-transfected Jurkat cells. In contrast, membrane-permeable late apoptotic neutrophils exhibited strong CRP binding, which comprised both Ca2+-dependent and heparin-inhibitable Ca2+-independent components. However, there was no effect of CRP binding upon phagocytosis of late apoptotic neutrophils by macrophages. CONCLUSION: Potential apoptotic cell opsonins such as CRP may bind only to intracellular structures in cells with leaky membranes that have progressed to a late stage of apoptosis.

Journal Article↗

PubMed1992

[A new concept of atherogenesis: the role of oxygen radicals].

The author discusses a new concept of atherogenesis which is based on older hypotheses (lipid infiltration hypothesis), theory of impaired endothelial barrier, role of immunological and thrombocytic factors) and supplements it by new findings on the role of oxygen radicals in the development of atherosclerosis. The atherogenity of native low density lipoproteins (LDL) is enhanced substantially by their post-secretory changes caused by the action of free oxygen radicals on unsaturated fatty acids in the outer layer of LDL particles. The development of lipid peroxides on the surface of LDL leads to a changed orientation of the metabolism of LDL particles: oxidized LDL are not bound to classical LDL receptors in the liver but to so-called scavenger receptors in monocytes and macrophages. Lipid accumulation in monocytes, not controlled by feedback mechanisms, leads to formation of foam cells which are the basis of atheromatous plaques. This process can be influenced by antioxidants which block the formation of lipid peroxides. The new concept is particularly important for the population of Czechoslovakia and other formerly totalitarian countries where deterioration of the environment occurred and concurrently also adverse dietary changes (high fat, sucrose and spirit intake, low vegetable and fruit consumption). It is probable that an increased intake of antioxidants (ascorbic acid, carotenes, tocopherols, bioflavonoids, selenium etc.) would, along with other corrective provisions, suppress the steep increase of cardiovascular diseases.

Arteriosclerosis↗

PubMed2005

Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease): evidence for a dendritic cell derivation?

Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease is a rare histiocytic disorder of unknown origin. Both dendritic cell and monocyte-macrophage lineage have been considered as the origin of the histiocytes that are classical of the disorder. We analyzed seven cases of Rosai-Dorfman disease to determine the immunophenotypic profile of these cells. Immunohistochemical analysis was undertaken by using: (a) fascin as a novel mature dendritic cell marker; (b) S-100 protein; (c) CD68 (both KP1 and PGM1) as macrophage related markers; (d) CD79a and (e) CD3. The Rosai-Dorfman histiocytes exhibited strong cytoplasmic staining for fascin in all the cases and demonstratedformation of a meshwork of fine dendritic processes emanating from the cell cytoplasm. S-100 protein was uniformly expressed in all the cases. Expression of both KP1 and PGM1 epitopes of CD68 was found to be weak and variable. The phagocytosed lymphocytes were composed of an admixture of both B and T-lymphocytes. The characteristic expression pattern of the histiocytes for fascin along with co-expression of S-100 protein and a consistently weaker and variable expression of macrophage-lineage markers point more towards a dendritic cell ontogeny of these cells. Further, abundant fascin expression and presence of dendritic processes indicate a differentiated or mature dendritic cell phenotype for these cells.

Adolescent↗

PubMed1986

Analysis of cellular and membrane extracts of human leukocytes from rheumatoid arthritis patients using two-dimensional electrophoresis.

Peripheral blood leukocytes from 30 patients with classic or definite rheumatoid arthritis (RA) and 18 healthy controls were separated into lymphocytes, monocytes and granulocytes and labelled with 35S-methionine. The integral membrane proteins with an amphiphilic nature were separated from hydrophilic proteins by use of the nonionic detergent Triton X-114. Both whole cells and membrane proteins were isotope labelled and separated by high resolution two-dimensional electrophoresis under denaturing conditions. Polypeptide spots were visualised by autoradiography. No consistent differences were found when leukocytes from RA patients were compared to the controls.

Arthritis, Rheumatoid↗

PubMed1986

[Evaluation of the Coulter Counter S+IV LMG: estimation of the leukocyte formula. Comparison with microscopic methods].

The evaluation of a differential count instrument of the Coulter S+line, the S+IV LMG Coulter-Counter, in particular for the lymphocyte, monocyte and granulocyte count was carried out. This differential analysis was compared with more classical methods of the manual (microscope) or automatic type (image analyser, Hematrack 360 type, Geometric Data). The repeatability is very good and the correlations excellent. The instrument can even detect the presence of low percentages of abnormal cells. Placement of reagents and samples at room temperature is important and the samples can be kept at room temperature for at least 9 hours without disturbing the count. In addition, energetic shaking of the samples does not change the count for the three types of cells. Due to the alarms given by the instrument as regards the cell distributions and all of the parameters of the blood cell count, no pathology should be ignored. In their laboratory, the authors note that about 25% of the smears are further examined by microscope.

Autoanalysis↗

PubMed1981

Biologic activities of bovine IgG subclasses.

With regard to our studies on the functional properties of bovine IgG1 and IgG2 antibodies, the differences were minimal when homologous systems were evaluated. Both IgG1 and IgG2 fixed bovine complement by the classical pathway, caused homologous passive cutaneous anaphylaxis, caused phagocytosis of coated erythrocytes by cultured monocytes and precipitated with an antigen having multiple unique determinants (ovalbumin). In contrast to IgG2, IgG1 caused neither adherence nor phagocytosis by freshly isolated neutrophils and monocytes. Additionally, IgG2 antibodies to DNP precipitated with DNP19ovalbumin while IgG1 antibodies formed soluble complexes with this antigen.

Anaphylaxis↗

PubMed1998

Modulation of T cell and monocyte function in the spleen following infection of pigs with African swine fever virus.

Infection of pigs with many strains of African Swine Fever Virus (ASFV) has been shown to cause a loss or marked decrease in the ability of splenocytes to respond to mitogens. These observations have been extended by cell fractionation and reconstitution experiments to show that the mitogen stimulated proliferative capacity of both the CD4+ and CD8+ T cells is affected. Similarly, monocytes which are directly infectable by virus, are functionally defective as antigen presenting cells when added to mitogen stimulated normal T cells. Interestingly, the same T cells which respond poorly in mitogenic assays can be activated by stimulation through the CD3 receptor. In contrast to the defective mitogenic response of T cells, B cell function, as assessed by stimulation through the CD40 ligand in vitro remains intact. There is no evidence for apoptosis in either the T cells or the B cells recovered from the spleens of ASFV infected animals 1-5 days following infection. Although the number of leucocytes which can be recovered from the infected spleen decreases rapidly with progression of the disease, the proportion of the different cell phenotypes remains constant. Thus decreased activity of lymphocytes in lymphoid tissue from ASFV infected animals appears to be directly attributable to infection of the monocytes.

African Swine Fever Virus↗

PubMed1990

Characterization and isolation of a C-reactive protein receptor from the human monocytic cell line U-937.

Human C-reactive protein (CRP) is an acute phase reactant that is opsonic and an activator of macrophage tumoricidal function. CRP also activates the classical C cascade. These activities suggest that CRP might interact with monocytes/macrophages via specific receptors in a manner analogous to the interaction of IgG with FcR. With the use of radio-labeled human CRP, we have observed specific binding of CRP to human blood monocytes and the human monocytic cell line U-937. Binding was saturable at a pathophysiologic concentration of CRP, with an estimated KD of 9.5 x 10(-8) M and 3.6 x 10(5) binding sites/cell. Specific binding was inhibited by polyclonal human IgG as well as an IgG1 myeloma. In the converse experiment, CRP failed to inhibit specific [125I]IgG binding. The mAb IV.3, which inhibits binding of IgG immune complexes to FcRII, did not inhibit CRP binding. A 100-fold excess of phosphorylcholine or the phosphorylcholine binding peptide of CRP (residues 47-63) failed to inhibit binding. Although human rIFN-gamma and PMA increased FcRI expression, these reagents had no affect on CRP receptor expression. A single membrane protein of 38 to 41 kDa from U-937 cells was chemically cross-linked to [125I]CRP; the cross-linking was inhibited by human IgG1 but not the IV.3 mAb. Furthermore, two membrane proteins with a Mr of 38 to 40 kDa and 58 to 60 kDa were isolated by CRP ligand-affinity chromatography. These proteins were of a distinct size from those isolated for FcRI from an IgG ligand matrix. These studies demonstrate specific binding of human CRP to a human monocytic cell line via receptors that are distinct from the IgG FcR and implicate CRP in nonspecific, preimmune host defense reaction mediated by cells of the monocytic lineage.

C-Reactive Protein↗

PubMed2005

IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS initiated by autoreactive CD4(+) T cells. EAE classically presents with a progressive ascending paralysis and is a model of multiple sclerosis that recapitulates some aspects of the disease. In this report we describe a mouse strain that spontaneously develops a severe, nonclassical form of EAE with 100% incidence. The distinct clinical phenotype is marked initially by a slight head tilt, progressing to a severe head tilt, spinning, or a rotatory motion. Classical EAE spontaneously occurs in myelin basic protein (MBP)-specific TCR transgenic RAG-1(-/-) mice (referred to as T/R(-)), whereas nonclassical EAE spontaneously occurs in T/R(-) IFN-gamma(-/-) mice (T/R(-)gamma(-)). Thus, the TCR recognizes the same Ag (MBP) and uses identical TCR in both cases. The cellular infiltrate in nonclassical EAE is predominantly found in the brainstem and cerebellum, with very little inflammation in the spinal cord, which is primarily affected in classical disease. Importantly, depending on the genetic makeup and priming conditions of the MBP-specific T cells, nonclassical disease can occur in the presence of an inflammatory infiltrate with eosinophilic, neutrophilic, or monocytic characteristics. Finally, we believe that nonclassical spontaneous EAE could be a useful model for the study of some characteristics of multiple sclerosis not observed in classical EAE, such as the inflammatory responses in the brainstem and cerebellum that can cause vertigo.

Animals↗

PubMed1979

Glucocorticoid receptors and effects in human lymphoid and leukemic cells.

A variety of human leukopathic diseases including human acute lymphoblastic leukemia are responsive to glucocorticoids in a varying proportion of cases. We identified specific glucocorticoid receptors in human acute lymphoblastic leukemia cells. Their presence or absence was well correlated with both in vivo and in vitro responsiveness of these target cells to glucocorticoids. These data suggest that knowledge of glucocorticoid receptor status in human acute lymphoblastic leukemia may aid in selecting patients for therapy. Furthermore, these receptors exhibit significant quantitative differences in various subtypes of human leukemia, with null-cell lymphoblastic leukemia having approximately three times the mean number of receptors per cell as T-cell leukemias. These differences in receptor levels are associated with major differences in complete remission duration independent of other prognosticators of response such as patient age, white count, and cell surface markers. Specific receptors for glucocorticoids can also be identified in normal human peripheral blood monocyte fractions including unpurified peripheral blood lymphocytes, T, and non-T subcomponents of circulating lymphocytes and circulating monocytes. By criteria of quantity, of binding affinity, and specificity, these receptors appear to be similar to other classical glucocorticoid receptors. Receptors in human peripheral blood lymphocytes may be induced threefold on a per cell basis by treatment with the mitogen phytohemagglutinin. This is associated with a marked increase in glucocorticoid responsiveness.

Cytoplasm↗