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PubMed1990

Stereologic analysis of monocytes and their subcellular organelles in patients with acute monocytic and myelomonocytic leukemia.

The stereologic characteristics of monocytes from patients with acute nonlymphocytic leukemia containing a monocytic component (FAB M4 and M5), and the monocytes from normal individuals were determined by morphometric analysis. The cells studied were monocytic cells beyond the promonocyte stage of development, as defined by ultrastructural criteria. Parameters evaluated included cell and nuclear volumes and surface areas, mitochondrial and myeloperoxidase (MPO)-positive secretory granule volume and numerical density as well as volume and number of the organelles/cell. Peripheral blood and bone marrow monocytes of leukemic patients could not be distinguished by their cell or organelle stereologic characteristics. Monocytes from patients with both M4 and M5 acute leukemia had relatively large cell and nuclear volumes. Mitochondrial volume density and volume/cell were also high in monocytes from leukemic patients (M4; 21 microns 3/cell, M5 20 microns 3/cell) as compared with monocytes from normal individuals (8.5 microns 3/cell). On the other hand, MPO-positive secretory granule stereologic parameters in monocytes from leukemic patients were indistinguishable from those of normal individuals. A small number (3 of 18) patients showed very low monocyte MPO-positive granule volume densities. There was a slight positive correlation between MPO-positive granule volume density and patient survival time. No relationship between mitochondrial characteristics and survival was noted.

Adult↗
PubMed1985

Monocyte inhibition of lung fibroblast growth: relationship to fibroblast prostaglandin production and density-defined monocyte subpopulations.

Mononuclear cell fibroblast interactions in the normal human lung are poorly understood. Mononuclear cells can regulate fibroblast function and blood monocytes are known to migrate to the lung and participate in pulmonary inflammation. Thus, to clarify mononuclear cell-fibroblast interactions in the normal lung, we obtained supernatants from adherent monocytes and characterized their effect on the log phase growth of human lung fibroblasts. Monocyte supernatants inhibited fibroblast growth in a dose-dependent fashion. The inhibition was the result of an approximately 16,000 MW soluble factor(s) that was heat stable, trypsin sensitive, and chymotrypsin resistant. Elaboration of the factor(s) required monocyte protein synthesis and was not restricted to a density-defined monocyte subpopulation. The inhibitory capacity of a monocyte supernatant was directly related to its ability to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by monocyte supernatants. Thus, monocyte inhibition of fibroblast growth may be mediated by fibroblast prostaglandin production. Recruitment of monocytes to the lung and subsequent monocyte inhibition of fibroblast growth may be important in regulating pulmonary fibrosis.

Cell Division↗
PubMed1985

Human monocyte-mediated cytotoxicity against herpes simplex virus-infected cells: activation of cytotoxic monocytes by free and liposome-encapsulated lymphokines.

Human peripheral blood monocytes were incubated with free or liposome-encapsulated human lymphokines containing macrophage-activating factor (MAF) and tested for their effect on herpes simplex virus (HSV)-infected target cells. Activated monocytes lysed allogeneic HSV type 2 (HSV-2)-infected whole human embryo cells and xenogeneic BALB/c mouse embryo cells (10E2) without any significant effect on uninfected cells, as measured by release of 51Cr from target cells after 18 h of cocultivation. Kinetic studies revealed that lysis of virus-infected cells occurred by 10 h following cocultivation with activated monocytes. The inability of free MAF or supernatants from MAF-activated monocytes to lyse HSV-2-infected cells suggested that direct monocyte-target cell contact is required for monocyte-mediated cytotoxicity of the virus-infected cells. Monocytes activated with MAF suppressed the production of HSV-2 and HSV-1 from virus-infected cells more than control monocytes did. In addition, monocytes treated with liposome-encapsulated MAF selectively destroyed HSV-2-infected cells but left uninfected cells unharmed. The capacity of liposome-encapsulated immunomodulators to activate human monocytes to selectively lyse HSV-2-infected cells has potential therapeutic benefit and should be evaluated in vivo.

Cells, Cultured↗
PubMed1985

Characterization of 3H-uridine incorporation and messenger RNA synthesis in human monocytes activated to secrete alpha interferon or monocyte-derived fibroblast growth factor.

Human monocytes are multifaceted cells with a wide range of immunoregulatory functions and distinct secretory products. This manuscript reports on initial attempts to identify specific early macromolecular synthetic events associated with various types of human monocyte activation by observing the patterns of RNA synthesis displayed by human monocytes that are exposed to well characterized activating stimuli. It was found that muramyl dipeptide (MDP), an activator of monocyte-derived fibroblast growth factor (MD-FGF) release from monocytes, also stimulates a reproducible increase in human monocyte total 3H-uridine incorporation and cytoplasmic messenger RNA (mRNA) synthesis at 4 h following activation. In contrast, polyriboinosinic acid:polyribocytidilic acid (poly I:C), an excellent stimulator of monocyte alpha interferon (IFN alpha) release, did not cause a change in either 3H-uridine incorporation or cytoplasmic mRNA production at any of the time points tested. Poly I:C was also found to be a poor stimulator of MD-FGF release. Conversely, MDP did not stimulate any detectable IFN release from human monocytes. The discrepancy between the patterns of macromolecular synthesis observed in human monocytes activated to secrete MD-FGF as compared with IFN indicates that divergent postactivation control mechanisms may be operative at the RNA level in the monocyte following activation of these two distinct functions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Modulation of T cell production of interferon-gamma by human monocytes: effect of engagement of CD14 on monocytes.

It has been suggested that CD14 might have influences on a variety of immunoregulatory functions of monocytes. The current studies therefore examined in detail the immunoregulatory roles of CD14 by studying the effects of anti-CD14 mAb. Anti-CD14 mAb suppressed the monocyte-dependent interferon-gamma (IFN-gamma) production by CD4+ T cells induced by soluble anti-CD3. Although anti-CD14 mAb also suppressed the IL-6 production by monocytes, the inhibition of the IFN-gamma production induced by soluble anti-CD3 was not restored by addition of exogenous IL-6 or factors generated from cultured monocytes. Of note, anti-CD14 mAb decreased the expression of CD54, but not that of CD11a or CD18, on monocytes, suggesting that inhibition of the soluble anti-CD3-induced IFN-gamma production by anti-CD14 mAb might be a result from decrease in CD11a/CD18-CD54-mediated interactions between CD4+ T cells and monocytes. By contrast, anti-CD14 mAb enhanced the IFN-gamma production by immobilized anti-CD3-activated CD4+ T cells in the presence of monocytes. This enhancement of the IFN-gamma production required physical contact between monocytes and T cells, which does not involve MHC class II antigen-CD4 interactions. These results indicate that CD14 on monocytes plays a variety of immunomodulatory functions depending upon the nature of stimulation. The data thus demonstrated the presence of several different interactions between monocytes and T cells that regulate the T cell cytokine production.

Antibodies, Monoclonal↗
PubMed1997

Monocyte chemoattractant protein-1 induces monocyte recruitment that is associated with an increase in numbers of osteoblasts.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine family of cytokines. The principal function of MCP-1 is thought to be the stimulation of monocyte recruitment. Monocyte products are potential regulators of bone cell activity. Growth factors produced by monocytes may stimulate bone formation, while cytokines such as IL-1 and IL-6 can induce bone resorption. To determine whether MCP-1 enhances recruitment of monocytes during bone healing, studies were carried out in which MCP-1 was applied to osseous sites in vivo. Changes in monocyte number were determined by immunohistochemistry using the antibody ED-1 specific for peripheral monocytic cells. The effect of MCP-1 on osteoblast number was determined by counting the number of alkaline phosphatase positive cells in close proximity to bone. For comparison, osteoblast number was also determined following stimulation with platelet-derived growth factor (PDGF)-BB plus IGF-1 in vivo. Results indicate that MCP-1 stimulated a large increase in monocyte recruitment compared to vehicle alone. An increase in monocytes induced by MCP-1 was associated with an increase in the number of osteoblasts lining the bone surface, although not to the same magnitude as a positive control, PDGF-BB, and IGF-1. These results indicate that MCP-1 induces the recruitment of monocytes to bone and suggest that the recruitment is associated with an increase in osteoblast number. This is likely to occur via indirect mechanisms, because MCP-1 did not directly enhance DNA synthesis in osteoblastic cells in vitro. Thus, activated mononuclear phagocytes may play an important role in osseous wound healing by stimulating proliferation of osteoblastic cells, presumably through the elaboration of growth factors.

Alkaline Phosphatase↗
PubMed1992

Interactions between human monocytes and tumour cells. Monocytes can either enhance or inhibit the growth and survival of K562 cells.

Human bloodstream monocytes can kill cultured tumour cells (K562), as assessed by specific release of 51Cr from the targets and by inhibition of 3H-thymidine incorporation. Confluent monolayers of monocytes were required for maximal cytotoxicity, and the density of the K562 cells was also an important factor. For example, when K562 cells were seeded at high cell densities, they were killed during incubation with monocytes, but when seeded at low cell densities their growth and survival was enhanced during culture with monocytes. The factor(s) which promoted the survival and division of low density K562 cultures was endogenously secreted from monocytes as it was present in monocyte-conditioned medium, whereas the cytotoxic factor(s) were only expressed during co-culture of monocytes with K562 cells. Conditioned medium from HL 60, U-937, HeLa and K562 could also enhance the growth and survival of low density K562 cultures, and a similar effect was also observed upon the addition of catalase and superoxide dismutase to such cultures. Thus, the monocyte:target ratio is important in determining whether monocytes exhibit cytotoxic or growth-promoting effects and hence tumour-derived or monocyte-derived reactive oxidant species may play a role in tumour cell cycle regulation.

Catalase↗
PubMed2001

Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection.

UNLABELLED: The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19--PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling METHOD: Healthy neonates had significantly lower percentages of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+) monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.

Adult↗
PubMed2000

Monocyte chemoattractant peptide-1 expression during cutaneous allergic reactions in mice is mast cell dependent and largely mediates the monocyte recruitment response.

BACKGROUND: Macrophages and infiltrating monocytes comprise the largest population of cells within the airways of patients with allergic asthma. Both become activated and thus contribute to the pathologic features of allergic reactions, but the mechanism by which they are recruited has not been well documented. OBJECTIVE: Our purpose was to assess the role of the CC chemokine monocyte chemotactic peptide-1 (MCP-1) in monocyte recruitment during allergic reactions in mice. METHOD: We used immunohistochemistry and Northern blotting to assess MCP-1 expression, selective mast cell reconstitution of mast cell-deficient W/W(v) mice to demonstrate the mast cell dependence of MCP-1 expression and monocyte recruitment and neutralizing anti-MCP-1 antibodies to block monocyte recruitment during cutaneous allergic reactions. RESULTS: MCP-1 was expressed largely by resident dermal cells within the allergic lesions at 4 hours after challenge, followed within several hours by an influx of monocytes; at 10 hours after challenge monocytes comprised a substantial proportion of the infiltrating cells at the nidus of the response. Mast cell-reconstituted, but not mast cell-deficient W/W(v) mice expressed MCP-1 transcripts and developed monocyte infiltrates after allergen challenge. Finally, anti-MCP-1 antibody treatments reduced by approximately 63% the influx of monocytes into the reaction sites. CONCLUSIONS: These data clearly demonstrate the mast cell dependence of the MCP-1 expression and the monocyte influx and establish a substantial, but not exclusive, causal relationship between these 2 events.

Animals↗
PubMed1991

Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.

Base Sequence↗
PubMed1986

Fate of Chlamydia trachomatis in human monocytes and monocyte-derived macrophages.

The fate of Chlamydia trachomatis (L2/434/Bu) in human peripheral blood monocytes and human monocyte-derived macrophages was studied by transmission electron microscopy (TEM) and by measuring the yield of infectious C. trachomatis in one-step growth experiments. Two main types of phagosome were seen by TEM in the cytoplasm of C. trachomatis-infected human monocytes (1 h postinfection [p.i.]): one in which the elementary body (EB) was tightly surrounded by the membrane of the phagosome and another in which the EB appeared in an enlarged phagosome. Later, 24 to 48 h p.i., each phagosome contained a single EB-like particle, an atypical reticulate body, or a damaged particle. One-step growth experiments showed that infection of human monocytes with C. trachomatis results in a decrease of infectious particles between 24 and 96 h p.i., whereas infection of the monocytes by C. psittaci (6BC strain) results in productive infection with, however, a 3.5-log lower yield than in control MA-104 cells. In contrast to the abortive replication of C. trachomatis in monocytes, monocyte-derived macrophages permitted replication as indicated by one-step growth experiments and TEM. in C. trachomatis-infected, monocyte-derived macrophages 72 h p.i., inclusions of two kinds were observed by TEM. One was very similar to the typical inclusions appearing in infected MA-104 (control) cells; the other was atypical, pleomorphic, often contained "channels," and held relatively few EB and reticulate bodies, some of which appeared damaged or abnormal. The significance of the responses to infection with C. trachomatis in monocytes compared with monocyte-derived macrophages and the role of these cells in sustaining chronic or latent infection and in dissemination of the infection to various parts of the body is discussed.

Chlamydia trachomatis↗
PubMed1995

Phenotypic and functional changes in peripheral blood monocytes during progression of human immunodeficiency virus infection. Effects of soluble immune complexes, cytokines, subcellular particulates from apoptotic cells, and HIV-1-encoded proteins on monocytes phagocytic function, oxidative burst, transendothelial migration, and cell surface phenotype.

We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections. In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired. In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients. By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes. Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection.

Antigen-Antibody Complex↗
PubMed1997

Tumor necrosis factor alpha (TNFalpha) promotes growth of virulent Mycobacterium tuberculosis in human monocytes iron-mediated growth suppression is correlated with decreased release of TNFalpha from iron-treated infected monocytes.

The human immune response to Mycobacterium tuberculosis is not well characterized. To better understand the cellular immune response to tuberculosis, a human mononuclear phagocyte culture system using a low-infecting inoculum of M. tuberculosis to mimic in vivo conditions was developed. Using this system, monocytes treated with IFNgamma/TNFalpha/ calcitriol (CytD) were permissive for the growth of virulent M. tuberculosis. In the presence of iron, however, these monocytes suppressed the growth of M. tuberculosis. The enhanced permissiveness of CytD-preincubated monocytes was found to be due to TNFalpha, however, the ability of iron to suppress M. tuberculosis growth also required preincubation with TNFalpha. Iron-mediated growth suppression was correlated with selective suppression of TNFalpha release from infected monocytes. In addition, removal of TNFalpha from CytD-treated monocytes 2 d after infection mimicked the suppressive effect of iron, suggesting that iron may also be decreasing monocyte sensitivity to exogenously added TNFalpha. In the absence of iron, permissive, CytD-treated monocytes formed large infected cellular aggregates. With iron treatment, aggregation was suppressed, suggesting that the iron-suppressive effect on M. tuberculosis growth may be related to suppression of monocyte aggregation and diminished cell-to-cell spread of M. tuberculosis. The results of this study indicate that TNFalpha preincubation is required for human monocytes to exert an iron-mediated suppressive effect on M. tuberculosis growth. In the absence of iron, however, the continued presence of TNFalpha has a growth-promoting effect on M. tuberculosis in human monocytes. Iron may be an important early modulator of M. tuberculosis growth via its effects on TNFalpha.

Adult↗
PubMed2003

Dendritic cell differentiation potential of mouse monocytes: monocytes represent immediate precursors of CD8- and CD8+ splenic dendritic cells.

The monocyte capacity to differentiate into dendritic cells (DCs) was originally demonstrated by human in vitro DC differentiation assays that have subsequently become the essential methodologic approach for the production of DCs to be used in DC-mediated cancer immunotherapy protocols. In addition, in vitro DC generation from monocytes is a powerful tool to study DC differentiation and maturation. However, whether DC differentiation from monocytes occurs in vivo remains controversial, and the physiologic counterparts of in vitro monocyte-derived DCs are unknown. In addition, information on murine monocytes and monocyte-derived DCs is scarce. Here we show that mouse bone marrow monocytes can be differentiated in vitro into DCs using similar conditions as those defined in humans, including in vitro cultures with granulocyte-macrophage colony-stimulating factor and interleukin 4 and reverse transendothelial migration assays. Importantly, we demonstrate that after in vivo transfer monocytes generate CD8- and CD8+ DCs in the spleen, but differentiate into macrophages on migration to the thoracic cavity. In conclusion, we support the hypothesis that monocytes generate DCs not only on entry into the lymph and migration to the lymph nodes as proposed, but also on extravasation from blood and homing to the spleen, suggesting that monocytes represent immediate precursors of lymphoid organ DCs.

Animals↗
PubMed2006

Attractin, a dipeptidyl peptidase IV/CD26-like enzyme, is expressed on human peripheral blood monocytes and potentially influences monocyte function.

The ectoenzyme dipeptidyl peptidase IV (DP IV; CD26) was shown to play a crucial role in T cell activation. Several compounds inhibiting DP IV-like activity are currently under investigation for the treatment of Type 2 diabetes, rheumatoid arthritis, colitis ulcerosa, psoriasis, multiple sclerosis, and other diseases. In the present study, we show that human peripheral blood monocytes express a DP IV-like enzyme activity, which could be inhibited completely by the synthetic DP IV inhibitor Lys[Z(NO(2))]-thiazolidide. DP IV immunoreactivity was not detectable on monocytes, and DP IV transcript levels of monocytes were near the detection limit of quantitative polymerase chain reaction. However, monocytes exhibit a strong mRNA expression of the multifunctional DP IV-like ectoenzyme attractin and were highly positive for attractin in flow cytometric analysis. Fluorescence microscopy clearly demonstrated that attractin is located on the cell surface of monocytes. Attractin immunoprecipitates hydrolyzed Gly-Pro-pNA, indicating that monocyte-expressed attractin possesses DP IV-like activity. Inhibitor kinetic studies with purified human plasma attractin revealed that Lys[Z(NO(2))]-thiazolidide not only inhibits DP IV but also attractin (50% inhibition concentration=8.45 x 10(-9) M). Studying the influence of this inhibitor on monocyte functions, we observed a clear reduction of cell adhesion to fibronectin-coated culture plates in the presence of Lys[Z(NO(2))]-thiazolidide. Moreover, this inhibitor significantly modulates the production of interleukin-1 (IL-1) receptor antagonist, IL-6, and transforming growth factor-beta1 in lipopolysaccharide-stimulated monocyte cultures. In summary, here, we demonstrate for the first time expression of attractin on monocytes and provide first data suggesting that drugs directed to DP IV-like enzyme activity could affect monocyte function via attractin inhibition.

Adenosine Deaminase↗
PubMed2005

Monocyte adhesion to xenogeneic endothelium during laminar flow is dependent on alpha-Gal-mediated monocyte activation.

Monocytes are the predominant inflammatory cell recruited to xenografts and participate in delayed xenograft rejection. In contrast to allogeneic leukocytes that require up-regulation of endothelial adhesion molecules to adhere and emigrate into effector tissues, we demonstrate that human monocytes adhere rapidly to unstimulated xenogeneic endothelial cells. The major xenoantigen galactosealpha(1,3)galactosebeta(1,4)GlcNAc-R (alpha-gal) is abundantly expressed on xenogeneic endothelium. We have identified a putative receptor for alpha-gal on human monocytes that is a member of the C-type family of lectin receptors. Monocyte arrest under physiological flow conditions is regulated by alpha-gal, because cleavage or blockade results in a dramatic reduction in monocyte adhesion. Recruitment of human monocytes to unactivated xenogeneic endothelial cells requires both alpha(4) and beta(2) integrins on the monocyte; binding of alpha-gal to monocytes results in rapid activation of beta(2), but not alpha(4), integrins. Thus, activation of monocyte beta(2) integrins by alpha-gal expressed on xenogeneic endothelium provides a mechanism that may explain the dramatic accumulation of monocytes in vivo.

Animals↗
PubMed1992

Regulation of the expression of ICAM-1 on human monocytes and monocytic tumor cell lines.

In this study we investigated the mechanisms regulating expression of ICAM-1 that plays an important role for Ag presentation, on peripheral blood monocytes, and three myelomonocytic cell lines representing different stages of monocyte maturation. ICAM-1 expression on freshly isolated monocytes was low in all donors tested. After 16- to 20-h incubation, about a 20-fold increase was observed, whereas ICAM-1 expression on lymphocytes did not change. This marked increase in Ag expression was specific for ICAM-1, because expression of other monocyte Ag remained unchanged (alpha-chain of lymphocyte function-associated Ag-1) or decreased (ICAM-2, alpha-chains of CR3 and CR4, their common beta-chain and Fc gamma RI) during overnight incubation; only HLA-DR showed a slight increase. Enhanced expression of ICAM-1 was not caused by adherence; it was also not due to trace amounts of IFN-gamma possibly present under our culture conditions. Endotoxin contamination of the medium was excluded as a cause for the enhanced expression, and neither LPS nor its antagonist polymyxin B were able to alter ICAM-1 expression. Whole blood culture almost completely prevented up-regulation of ICAM-1 expression, thus apparently mimicking the in vivo situation. Culture of monocytes together with other PBMC had no significant influence on monocyte ICAM-1 levels. From 12 different cytokines tested for their ability to modulate "spontaneous" up-regulation of ICAM-1 in culture, only IFN-gamma was found to increase expression about twofold. This effect was also observed in whole blood culture. All other cytokines had no significant effect. In contrast, ICAM-1 expression on two of the three cell lines (KG1 and HL60) was inducible by TNF-alpha to a much higher degree than by IFN-gamma, whereas the results with U937 were comparable with those obtained for normal monocytes. The protein- and RNA-synthesis inhibitors cycloheximide and actinomycin D prevented expression of ICAM-1 in a dose-dependent fashion. In Northern blot experiments no difference in the amounts of mRNA was observed between freshly isolated and cultured monocytes, indicating that "spontaneous" induction of ICAM-1 is regulated at a posttranscriptional level. In contrast, stimulation with IFN-gamma caused a significant increase of detectable RNA comparable to that observed for Ag expression. These results disclose a very special regulation of ICAM-1 expression on monocytes which could be consistent with the view that ICAM-1 is actively down-regulated in vivo until the monocyte leaves the circulation.

Antigens, CD↗
PubMed1985

Inhibitory effect of monocyte reactive antibodies on monocyte chemotaxis in systemic lupus erythematosus.

Presence of different types of autoantibodies is a basic feature of systemic lupus erythematosus (SLE). Though monocytes, macrophages play an important role in cellular immunity, autoantibodies against monocytes have not been sufficiently studied. The authors used automatic fluorochromatic assay to detect monocyte reactive autoantibodies in the sera of SLE patients. Of SLE 35.5% sera showed complement-mediated monocytotoxic activity against healthy monocytes. Monocyte reactive SLE sera as well as monoclonal antibodies against human monocytes inhibited chemotaxis of control monocytes. The results suggest that monocyte reactive autoantibodies may play a role in the decreased monocyte number and defective monocyte functions observed in SLE.

Antibodies, Monoclonal↗