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PubMed1981

[Study of monocyte function in patients with cervical cancer by using T-lymphocyte monocyte interaction in response to phytohemagglutinin (author's transl)].

Monocytes have been thought to play an important role in the immune surveillance system of cancer patients since monocytes were shown to participate as accessory cells in the induction of T-cell proliferation to PHA by Potter et al. in 1977. We had already reported the depression of monocyte function with the progress of cancer after PHA response of mononuclear cells obtained by centrifugation of Ficoll-Hypaque and lymphocytes obtained by depletion of monocytes ingesting Silica from mononuclear cells was compared in cancer patients. In that study, however, monocyte function was considered not to be indicated truly because responding cells were different at each examination. Therefore, in this study responding cells were graded as T-cells obtained from healthy volunteers and monocytes were added to the T-cells. Monocyte function in this study was as follows: PHA response to T-cells and monocytes over PHA response to T-cells. In this study, monocytes were allogenic to T-cells. At first, the influence of monocytes to allogenic T-cells was studied but it was found to be negligible. The ratio of monocytes and T-cells was 1:1. The concentration of PHA was 20 micrograms/ml. Finally, the monocyte function of patients with cervical cancer was studied. It was increased at the stage of CIS and then gradually decreased. At the advanced stage, it was significantly decreased to comparison with that of healthy volunteers.

Cell Communication↗
PubMed1995

Differential effects of anti-inflammatory cytokines (IL-4, IL-10 and IL-13) on tumoricidal and chemotactic properties of human monocytes induced by monocyte chemotactic and activating factor.

The effect of recombinant human IL-4, IL-10, and IL-13 on the chemotaxis and antitumor activity of human blood monocytes induced by monocyte chemotactic and activating factor (MCAF) was examined. MCAF alone did not induce monocyte-mediated cytotoxicity against human melanoma (A375-M) cells whereas it significantly enhanced the cytotoxicity by norMDP-stimulated monocytes. MCAF, unlike IFN-gamma, had no priming effect on monocyte activation by norMDP. MCAF acted with norMDP or LPS to enhance the production of both IL-1 beta and TNF-alpha. Enhanced cytotoxicity of monocytes stimulated with MCAF plus norMDP was reduced by IL-1 receptor antagonist and anti-TNF-alpha antibody. IL-4, IL-10, and IL-13 suppressed the generation of antitumor activity and cytokine production (IL-1 beta and TNF-alpha) of monocytes stimulated with MCAF plus norMDP or LPS. Chemotaxis of monocytes induced by MCAF was not affected by norMDP or any of the anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Moreover, the pretreatment of monocytes with anti-inflammatory cytokines did not suppress monocyte-chemotaxis. These findings suggest that in vivo recruitment and anti-tumor expression of blood monocytes induced by MCAF may be differently regulated by anti-inflammatory cytokines in vivo.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Lipopolysaccharide (LPS) modulation of human monocyte accessory cell function in promoting T-cell colonies: inability of LPS and IL-1 to abrogate the need for monocytes with high HLA-DR expression.

The abilities of human monocytes differentially expressing HLA-DR and of lipopolysaccharide (LPS) to influence T-cell colony responses were investigated. Optimal T-cell colony responses stimulated by soluble Staph protein A were crucially dependent on monocytes. Also, monocyte facilitation of colony responses was markedly inhibited by 10 micrograms/ml LPS and the addition of indomethacin reversed this inhibition. In contrast the inhibition of T-cell colony responses with 100 micrograms/ml LPS was not reversed with indomethacin and preincubation experiments with high concentrations of LPS showed the inhibition could be mediated through T cells by mechanisms other than prostaglandins. The treatment of monocytes with a monoclonal anti-HLA-DR reagent + C reduced the frequencies of monocytes expressing high levels of HLA-DR approximately fivefold and the resulting monocytes which expressed low levels of HLA-DR also poorly functioned in the promotion of colony responses compared to controls. LPS in the presence of indomethacin improved the ability of monocytes expressing low levels of HLA-DR to promote colony responses. However, these monocytes consistently failed to augment colony responses to those levels observed with untreated monocytes and their failure was not secondary to deficient interleukin 1 release. These results indicate that although LPS can somewhat potentiate the accessory cell function of certain human monocytes, it cannot abrogate an additional requirement for those monocytes expressing high levels of HLA-DR.

Adult↗
PubMed1995

Monocytes from patients with combined hypercholesterolemia-hypertriglyceridemia and isolated hypercholesterolemia show an increased adhesion to endothelial cells in vitro: II. Influence of intrinsic and extrinsic factors on monocyte binding.

One of the primary risk factors for atherosclerosis is hypercholesterolemia. Patients with isolated hypercholesterolemia or combined hypercholesterolemia-hypertriglyceridemia are at risk to develop premature atherosclerosis. Diet-induced hypercholesterolemia in animals leads to an increased adhesion of monocytes to and transmigration through the intact endothelium of the vessel wall. In the present study, we investigated in vitro binding of freshly isolated monocytes from patients and healthy controls to a monolayer of endothelial cells obtained from human umbilical vein. All four diagnosed patient groups with isolated or combined hypercholesterolemia showed a significant increase in monocyte binding as compared with the control group (familial hypercholesterolemia [FH], +41%; polygenic hypercholesterolemia [PH] +35%; familial combined hypercholesterolemia [FCH], +47%; nonfamilial combined hypercholesterolemia-hypertriglyceridemia [CHH], +67%). In a longitudinal study it was observed that diet or medication induced a decrease in cholesterol and triglycerides; however, these therapeutic conditions did not diminish in vitro monocyte binding in the patient groups. There was no correlation between monocyte binding and plasma cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, or lipoprotein(a) within hyperlipidemic patient groups. The presence of heart and vessel disease in hyperlipidemic patients was not associated with a change in monocyte binding. The adhesion to endothelial cells of monocytes from smoking patients with combined hypercholesterolemia (27%) was significantly higher (+23%) than that of monocytes from nonsmoking patients. Cytofluorimetric analysis of monocytes from FCH and CHH patients for specific monocyte differentiation markers and integrins did not show differences as compared with monocytes from healthy controls.

Cell Adhesion↗
PubMed2006

Soy isoflavones attenuate human monocyte adhesion to endothelial cell-specific CD54 by inhibiting monocyte CD11a.

Soy-based diets have been shown to protect against the development of atherosclerosis; however, the underlying mechanism(s) remain unknown. Interaction between activated monocytes and inflamed endothelial cells is an early event in atherogenesis. Therefore, we examined whether treatment of monocytes with soy phytochemicals could inhibit their adhesion to the endothelial cell-specific protein, CD54, a key factor in monocyte adhesion. Female Sprague-Dawley rats were fed AIN-93G diets containing soy protein isolate or casein. Sera from soy-fed rats inhibited CD54-dependent monocyte adhesion, whereas sera from casein-fed rats did not. To determine whether isoflavones in the sera of soy-fed rats were involved in this inhibition, monocytes were preincubated with soy isoflavones. Isoflavone treatment inhibited monocyte adhesion to CD54 protein, as well as to endothelial cells expressing CD54. Monocyte expression of CD11a, the cognate receptor for CD54, was unaffected by isoflavones. However, binding of the activation epitope-specific antibody mAb24, which binds specifically to the active form of CD11a, was significantly lower in soy isoflavone-treated monocytes than in media-treated cells. These findings suggest that inhibition of CD54-dependent monocyte adhesion by soy isoflavones is mediated in part by affinity regulation of CD11a. Inhibition of monocyte adhesion to endothelial cells by isoflavones resulted in reduced expression of the inflammatory cytokines IL-6 and IL-8. Collectively, these data suggest that the athero-protective effect of soy diets may be mediated by blocking monocyte-endothelial cell interaction.

Animals↗
PubMed1991

Lactoferrin inducible monocyte cytotoxicity defective in esterase deficient monocytes.

We recently demonstrated a higher incidence of monocyte esterase deficiency in patients with lymphoproliferative neoplasia and gastrointestinal carcinoma than in the normal population. Using lactoferrin to stimulate monocyte cytotoxicity we have now compared the abilities of esterase positive and esterase deficient monocytes to lyse K562 cells. The esterase deficient monocytes were from normal subjects whose monocytes have consistently failed to show cytochemical esterase staining over 30-72 months and which lack specific monocyte isoenzymes. The esterase positive monocytes were from age and sex matched control subjects. Esterase positive monocytes responded to lactoferrin stimulation by a five-fold increase in cytotoxicity whereas deficient monocytes failed to produce any response. These results indicate a possible defect in cytotoxicity of esterase deficient monocytes and together with the epidemiological findings suggest a link between monocyte esterase deficiency and neoplasia.

Cells, Cultured↗
PubMed2003

Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients.

Leptin, the 16 kDa product of the ob gene, is a an adipocyte-secreted hormone that centrally regulates weight. However, the physiological role of leptin is not limited to the regulation of food intake and energy expenditure, and leptin has a variety of effects in peripheral tissues, such as a regulatory role modulating the immune system. Thus, leptin receptor is expressed in human peripheral blood mononuclear cells, mediating the leptin stimulation of proliferation and activation, the production of proinflammatory cytokines from cultured monocytes, and the prevention of apoptotic death in serum-deprived monocytes. Because leptin can stimulate monocytes and the production of reactive oxygen species (ROS) are the result of monocyte activation, we investigated the effect of leptin on ROS production by human monocytes in vitro. Oxidative burst was measured by oxidation of the redox-sensitive dye 2',7'-dichlorofluorescein diacetate, and analysed by flow cytometry. We have found that stimulation with leptin produces oxygen radical formation by monocytes. This effect is dependent on the dose and maximal response is achieved at 10 nM leptin. Because HIV infection induces the production of ROS, we next investigated the effect of leptin on ROS production in monocytes from HIV-positive (HIV+) subjects. We have also found that monocytes from HIV+ subjects spontaneously produced increased amounts of free radicals. In contrast, leptin stimulation of monocytes from these patients partially inhibited the production of ROS. This effect of leptin was also dependent on the dose and maximal effect was achieved at 10 nM. The effect of leptin stimulating the production of ROS is consistent with the proinflammatory role in the immune system. On the other hand, the inhibitory effect on monocytes from HIV+ subjects may be explained by the attenuation of the oxidative burst by a delayed activation of monocytes in a hyperinflammatory state.

Adult↗
PubMed1998

Differential tropism and chemokine receptor expression of human immunodeficiency virus type 1 in neonatal monocytes, monocyte-derived macrophages, and placental macrophages.

Laboratory-adapted (LA) macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates (e.g., HIV-1(Ba-L)) and low-passage primary (PR) isolates differed markedly in tropism for syngeneic neonatal monocytes, monocyte-derived macrophages (MDMs), and placental macrophages (PMs). Newly adherent neonatal monocytes and cultured PMs were highly refractory to infection with PR HIV-1 isolates yet were permissive for LA M-tropic isolates. Day 4 MDMs were also permissive for LA M-tropic isolates and additionally, were permissive for over half the PR isolates tested. Qualitative differences in PR HIV-1 infection of monocytes/MDMs could not be correlated with CD4 levels alone, and in all three cell types the block to PR HIV-1 strain replication preceded reverse transcription. Neonatal monocyte susceptibility to PR HIV-1 strains correlated with increasing CCR-5 expression during maturation. CCR-5 could not be detected on newly adherent (day 1) neonatal monocytes, in contrast to adult monocytes (H. Naif et al., J. Virol. 72:830-836, 1998), but was readily detectable after 4 to 7 days of culture. However, moderate CCR-5 mRNA levels were present in day 1 neonatal monocytes and remained constant during monocyte maturation. CCR-5 was not detectable on the surface of PMs, yet the receptor was present within permeabilized cells. Notably, two brain-derived PR HIV-1 isolates from a single patient, differing in their V3 loops, were discordant in their abilities to infect neonatal monocytes/MDMs and PMs, yet both isolates could infect newly adherent adult monocytes. Together these data strongly suggest that LA HIV-1 isolates are able to infect neonatal monocytes at earlier stages of maturation and lower-level expression of CCR-5 than PR isolates. The differences between neonatal and adult monocytes in susceptibility to PR isolates may also be related to the level of CCR-5 expression.

Adult↗
PubMed2001

Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14.

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-alpha message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are "primed" for enhanced responsiveness to endotoxin with increased cytokine expression.

Animals↗
PubMed1998

Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentiation of blood monocytes in rat skin.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for blood monocytes in vitro. Recent studies in MCP-1-transgenic mice revealed that the local production of MCP-1 caused monocyte infiltration. However, the kinetics of monocyte infiltration after the production of MCP-1 or the amount of MCP-1 necessary for monocyte recruitment are not known. METHODS: We purified recombinant rat MCP-1 expressed in COS-7 cells, and injected it into rat skin. The infiltrating cells were examined by immunohistochemistry and ultrastructural peroxidase cytochemistry. RESULTS: Rat recombinant MCP-1 had a molecular mass of approximately 30 kD and exhibited the peak monocyte chemotactic activity at 10(-9) M. One microgram of MCP-1 caused intra- and extravascular accumulation of mononuclear cells 3 h after injection. The cells were ED1+, indicating they were blood monocytes. The infiltration of mononuclear cells peaked at 12-24 h, and most of them were TRPM-3+ and ED3+, characteristic to exudate macrophages. None of the cells expressed ED2 or Ki-M2R antigens, markers for resident macrophages, until 3 days after injection. There was no uptake of [3H]thymidine by the infiltrating cells. Ultrastructural peroxidase cytochemistry confirmed that the infiltrating cells were monocytes and exudate macrophages. The number of OX8+ lymphocytes also peaked at 12 h, consisting of approximately 9% of the total infiltrating cells. CONCLUSION: These results indicate that MCP-1 attracts blood monocytes as early as 3 h and the infiltrating monocytes differentiate into exudate macrophages in loco. However, this effect was transient and the infiltration of monocytes did not result in tissue damage.

Animals↗
PubMed1990

Expression of interleukin 2 receptors by monocytes from patients with acquired immunodeficiency syndrome and induction of monocyte interleukin 2 receptors by human immunodeficiency virus in vitro.

A population of circulating mononuclear cells from patients with AIDS was identified which expressed interleukin 2 receptors (IL-2R). By dual-fluorescence flow microfluorometry, the patients' IL-2R+ cells were further identified as Leu M3+ monocytes (29.4 +/- 5.2% of the Leu M3+ cells were IL-2R+, n = 15), whereas Leu M3+ monocytes from normal subjects were IL-2R negative (2.0 +/- 0.42%; P less than 0.001). By Northern analysis, monocytes from AIDS patients, but not control subjects, constitutively expressed steady-state levels of IL-2R mRNA. Functionally, the IL-2R+ monocytes were capable of depleting IL-2 from culture supernatants, suggesting a mechanism for the reduced IL-2 levels commonly seen in AIDS patients. IL-2R+ monocytes also expressed increased levels of surface HLA-DR which may favor monocyte T-cell interactions and the transmission of human immunodeficiency virus (HIV). In additional studies, normal monocytes were infected with a macrophage-tropic HIV isolate in vitro and monitored for IL-2R and HLA-DR expression. Within 24-48 h after exposure to HIV in vitro, but before evidence of productive infection, greater than 25% of the monocytes became IL-2R+ with increasing numbers of IL-2R+ cells and HLA-DR levels through day 6. These early signaling effects of HIV could be mimicked by adding purified HIV envelope glycoprotein gp120 to the monocytes. This stimulation of monocytes before or independent of productive infection of the cells by HIV is consistent with in vivo observations of activated and/or abnormal functions by monocytes that do not appear to be infected with HIV in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Synergistic enhancement of cytokine-induced human monocyte matrix metalloproteinase-1 by C-reactive protein and oxidized LDL through differential regulation of monocyte chemotactic protein-1 and prostaglandin E2.

C-reactive protein (CRP) and oxidized LDL (ox-LDL) are associated with inflammatory lesions, such as coronary artery disease, in which monocytes and matrix metalloproteinases (MMPs) may play a major role in the rupture of atherosclerotic plaques. Monocytes are recruited to inflammation sites by monocyte chemoattractant protein-1 (MCP-1), which may also participate in the activation of monocytes. The objective of this study was to compare the individual and combined effect of CRP and ox-LDL on human monocyte MMP-1 and the role of MCP-1 in this effect. Although CRP or ox-LDL failed to induce MMP-1 in control monocytes, these molecules enhanced MMP-1 production induced by tumor necrosis factor alpha (TNF-alpha) and granulocyte macrophage-colony stimulating factor (GM-CSF) with a synergistic increase in MMP-1 occurring in the presence of both mediators. Enhancement of MMP-1 by CRP and ox-LDL was attributable to a differential increase in MCP-1 and prostaglandin E2(PGE2). CRP, at physiological concentrations, induced high levels of MCP-1 and relatively low levels of PGE2, whereas ox-LDL caused a significant enhancement of PGE2 with little affect on MCP-1. Accordingly, CRP- and ox-LDL-induced MMP-1 production by monocytes was inhibited by anti-MCP-1 antibodies and indomethacin, respectively. Moreover, addition of exogenous MCP-1 or PGE2 enhanced MMP-1 production by TNF-alpha- and GM-CSF-stimulated monocytes. These results show that the combination of CRP and ox-LDL can cause a synergistic enhancement of the role of monocytes in inflammation, first, by increasing MCP-1, which attracts more monocytes and directly enhances MMP-1 production by activated monocytes, and second, by elevating PGE2 production, which also leads to higher levels of MMP-1.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta1 and beta2 integrins.

Human monocytes adhere to activated platelets, resulting in the formation of platelet-monocyte complexes (PMC). Complex formation depends on the interaction between platelet-displayed P-selectin and the specific ligand for P-selectin on leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have recently shown that monocytes within PMC have increased adhesive capacity to the activated endothelium. To better understand the effect of platelet binding on the capacity of monocytes to adhere to activated endothelium, the P-selectin-PSGL-1 interaction-induced changes in integrin functionality were studied. The binding of platelets to monocytes via P-selectin-PSGL-1 interactions was shown to increase expression and activity of alpha4beta1 and alphaMbeta2integrin, with a concomitant decrease in L-selectin expression. Furthermore, the binding of platelets to monocytes resulted in increased monocyte adhesion to intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and fibronectin. Platelet binding was also responsible for an increase in monocyte transendothelial migration. Similar effects were observed after engagement of PSGL-1 with specific antibodies or with P-selectin immunoglobulin protein. Our data suggest that platelets, by binding via P-selectin to PSGL-1 on monocytes, induce up-regulation and activation of beta1 and beta2integrins and increased adhesion of monocytes to activated endothelium. Hence, monocytes within PMC are in a higher state of activation and may have, therefore, an increased atherogenic capacity.

Antibodies↗
PubMed1992

Superantigen-mediated human monocyte-T lymphocyte interactions are associated with an MHC class II-, TCR/CD3-, and CD4-dependent mobilization of calcium in monocytes.

The present study was designed to examine the potential involvement of calcium ions as second messengers in the mediation of the staphylococcal enterotoxin A (SEA)/MHC class II-induced activation of human monocytes. Treatment of monocytes with a monomeric form of SEA failed to induce detectable changes in the level of intracellular calcium in either monocytes or THP-1 cells. However, cross-linking of SEA with biotin-avidin induced a rapid and transient increase in calcium levels in monocytes and in INF-gamma-treated THP-1 cells. This artificial cross-linking system was reproduced by natural physiologic ligands expressed on the surface of T lymphocytes. Delayed, transient, and concentration (cell as well as toxin)-dependent increases in the cytoplasmic level of free calcium in SEA-treated monocytes were observed upon the addition of autologous resting T cells or purified CD4+ cells, but not of CD8+ cells, B cells, or neutrophils. Antibodies against MHC class II Ag, TCR/CD3, and CD4 molecules inhibited the SEA-dependent interaction between monocytes and T cells as indicated by significant decreases in the rise of calcium levels observed in monocytes. Anti-CD8 and anti-class I antibodies did not affect the interaction between the monocytes and the T cells and failed to alter the calcium response. Taken together, these results suggest that the SEA-induced, T cell-dependent calcium mobilization in monocytes requires physical interactions between SEA-MHC class II, TCR/CD3, and CD4 molecules. The ability to mediate a T cell-dependent calcium increase in monocytes was shared by several enterotoxins including staphylococcal enterotoxin B and toxic shock syndrome toxin-1. The characteristics of the SEA-mediated calcium mobilization in monocytes strongly support the hypothesis that this response is an integral part of the signal transducing machinery linked to MHC class II molecules.

Antigens, Bacterial↗
PubMed1991

Regulation of fibronectin receptor (alpha 5 beta 1) mRNA expression in human monocytes and monocyte-derived macrophages by activation/differentiation signals.

Members of the beta 1 subfamily of integrins, a group of heterodimeric transmembrane adhesion receptors, mediate the attachment of monocytes and macrophages to cell matrix proteins such as fibronectin, collagen, and laminin. Such interactions are likely of considerable importance during inflammatory responses, when monocytes are recruited to, and retained in, extravascular sites. Because of the complexity of the interactions that befall monocytes during an inflammatory response, it seems likely that expression of adhesion receptors on monocytes would be precisely regulated. In the present study, we have examined the mRNA expression of alpha 5 and beta 1 subunits of the fibronectin receptor in purified human peripheral blood monocytes and monocyte-derived macrophages cultured in the absence or presence of various agents known to induce activation and/or differentiation. Incubation under nonadherent conditions for 6 h with interferon (IFN)-gamma or bacterial lipopolysaccharide (LPS) resulted in a decreased expression of both alpha 5 and beta 1 mRNAs in freshly isolated monocytes. In contrast, incubation with IFN-alpha did not result in a decreased expression of alpha 5 mRNA, although a moderate decrease in beta 1 mRNA was observed. Culture with granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, phorbol myristic acetate, or plasma fibronectin (under nonadherent and adherent conditions) did not result in a change in levels of alpha 5 or beta 1 transcripts. In contrast to the results obtained with freshly isolated monocytes, incubation for 6 h with IFN-gamma or LPS did not alter the expression of alpha 5 or beta 1 mRNA in macrophages derived by culture of monocytes for 6 days in Teflon beakers. Our results indicate that IFN-gamma and LPS, both of which may be present in inflammatory sites, downregulate the mRNA expression of fibronectin receptor subunits in monocytes. Moreover, alpha 5 and beta 1 gene regulation by these agents is apparently dependent on the differentiation stage of the cells. This may provide a mechanism by which extravasating monocytes detach from extracellular matrix proteins, present in subendothelial basement membranes and deposited in sites of inflammation, in order to pursue other activities.

Cell Differentiation↗
PubMed1983

Modulation of surface antigens of a human monocyte cell line, U937, during incubation with T lymphocyte-conditioned medium: detection of T4 antigen and its presence on normal blood monocytes.

The human monocyte line, U937, derived from an individual with histiocytic lymphoma, undergoes morphological and functional changes when incubated with medium conditioned by lectin-stimulated cloned human T lymphocytes. Using monoclonal antibodies and flow cytometry, we therefore analyzed alterations in surface components that might accompany these morphological changes, in comparison with components present on normal blood monocytes. The U937 cells possess three surface antigens in common with blood monocytes, detected with OKM1, 4F2, and anti-monocyte.2 (the last monocyte specific). DR antigen was not detectable on U937 cells with three anti-DR framework antibodies but was detected on blood monocytes. Unexpectedly, OKT4, a monoclonal antibody to T4 antigen previously believed to be restricted to helper T lymphocytes, also reacted with U937 cells. Six monoclonal antibodies to other epitopes on T4 also reacted with U937 cells. None of these could be inhibited by blocking of Fc receptors. T4 with its various epitopes were also expressed on normal human blood monocytes. Other lymphocyte surface markers (T3, T8, T6) and fibronectin were not detectable on U937 cells or monocytes. An individual, whose lymphocytes lacked the epitope detected with OKT4 but had epitopes detected with OKT4 A, B, C, and D, had monocytes with identical reactivity, evidence that the T4 on monocytes and lymphocytes are products of the same structural gene. Stimulation of U937 cells for 24 hours with supernatants from Con A-stimulated T lymphocyte clones caused an increase in expression of OKM1 and Fc receptor activity and a decrease in expression of T4, consistent with a more mature phenotype of blood monocytes. Although the function of the T4 molecule is unknown, it is notable that it is displayed by two cells of distinct lineage which interact in the response to soluble antigens.

Animals↗
PubMed1994

Production of IL-8 and monocyte chemotactic peptide-1 by peripheral blood monocytes. Disparate responses to phytohemagglutinin and lipopolysaccharide.

The temporal recruitment of leukocytes to a site of inflammation is dependent on a complex interplay of a number of soluble mediators. Recently, two families of chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL-8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family, which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit predominantly monocytes. Monocytes, after their arrival at a site of inflammation, could further amplify the immune response by secreting IL-8 and MCP-1. We sought to define conditions under which human peripheral blood monocytes produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner. However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by monocytes appeared to require de novo protein synthesis, in that cycloheximide blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells. However, treatment of monocytes with cycloheximide resulted in the superinduction of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased amounts of MCP-1 mRNA and protein. The addition of serum to culture media increased both the constitutive and PHA-induced production of monocyte-derived MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1 production by LPS. These findings suggest that distinct pathways of activation exist for the production of monocyte-derived IL-8 and MCP-1. The differential expression of these different but related polypeptides may offer a means of control of the type of immune cells that are recruited to a site of inflammation.

Base Sequence↗
PubMed1997

Monocyte recruitment and expression of monocyte chemoattractant protein-1 are developmentally regulated in remodeling bone in the mouse.

Tooth eruption is defined as the movement of a tooth from its site of development within the alveolar bone to its position of function in the oral cavity. It represents an excellent model to examine osseous metabolism as bone resorption and bone formation occur simultaneously and are spatially separated. Bone resorption occurs in the coronal (occlusal) area, whereas bone formation occurs in the basal area. Monocytes are thought to have a significant role in the regulation of osseous metabolism. The goal of this study was to examine the recruitment of monocytes to bone in C57BL/6J mice that are undergoing developmentally regulated bone remodeling. Monocytes were detected by immunohistochemistry and osteoclasts were counted as bone-associated multi-nucleated, tartrate-resistant acid phosphatase (TRAP)-positive cells. Cell numbers were obtained from histological sections of animals sacrificed daily for 14 days after birth; an image analysis system was used for quantification. The results demonstrated that, immediately after birth, there were relatively few monocytic cells. In the area of bone resorption, the number of monocytes increased with time, reaching peaks at 5 and 9 days, and decreased thereafter. A similar pattern was observed for osteoclasts. In the area of bone formation, there was a time-dependent increase in the number of monocytes. In contrast, the number of osteoclasts in this area was highest at the earliest time points and decreased after day 3. To investigate potential mechanisms for the recruitment of monocytes, expression of monocyte chemoattractant protein (MCP)-1 was assessed. The number of MCP-1-positive cells increased with time and was generally proportional to the recruitment of mononuclear phagocytes. Osteoblasts were the principal bone cell type expressing MCP-1. The results demonstrate that the recruitment of mononuclear cells in the occlusal area is associated with bone resorption. In contrast, recruitment of monocytes in the basal area is associated with bone formation and a decrease in the number of osteoclasts. These results suggest that monocytes have different functional roles in areas of bone formation compared with bone resorption. Furthermore, the expression of MCP-1 is developmentally regulated and may provide a mechanistic basis to explain the recruitment of monocytic cells.

Animals↗