Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOCYTES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 199 records · Page 11Linked to original sources
PubMed1982

In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen.

We demonstrated that the in vitro differentiation of human peripheral blood monocytes to macrophages is dependent on the environment and conditions of monocyte culture. Cultivation of monocytes on glass or microexudate-coated glass gave rise to cells resembling foreign body granuloma macrophages. After an initial rise in Fc receptor- and C3 receptor-mediated phagocytosis, a progressive loss of Fc receptor expression and C3-mediated ingestion were observed. The monocyte surface antigens recognized by the anti-human monocyte monoclonal antibodies 1D5 and 63D3 were lost from the surface of the majority of cells cultured on glass and microexudates. A subpopulation of Fc receptor-positive cells that were 1D5 and 63D3 positive was retained in fully differentiated cell populations. In comparison, monocytes cultivated on collagen matrices gave rise to highly phagocytic cells resembling human resident tissue macrophages. Both Fc- and C3-mediated phagocytosis were enhanced and remained so during the entire length of culture. The surface antigens recognized by the 1D5 antibody, expressed on all freshly seeded monocytes, was maintained on the macrophages. The antigen recognized by the 63D3 antibody was not expressed on mature cells. The present evidence would indicate that variations in expression of phagocytic receptors and the surface antigens 1D5 and 63D3 can be ascribed to the stage of development of the macrophage or its stage of activation, rather than to independent subsets of mononuclear phagocytes.

Antibodies, Monoclonal↗
PubMed1996

Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.

We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.

Adolescent↗
PubMed2002

Tubular cell-Escherichia coli interaction products modulate migration of monocytes through generation of transforming growth factor-beta and macrophage-monocyte chemoattractant protein-1.

BACKGROUND: Urinary tract infection is a common occurrence often associated with renal interstitial inflammation in the form of accumulation of mononuclear cells. We hypothesized that bacteria activate tubular cells to secrete cytokines, which may promote migration of mononuclear cells at the site of interaction. MATERIALS AND METHODS: We evaluated the migration of monocytes in response to tubular cell products (TC-S) and interaction products of E. coli with proximal tubular cells (TC-EC-S; concentrations of 5%, 10%, and 25%) using a modified Boyden chamber. To determine the molecular mechanism, we evaluated the effect of antibodies against macrophage-monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) on E. coli-tubular cell interaction product-induced migration of monocytes. In addition, we studied the effect of free-radical scavengers on activation of tubular cells. RESULTS: The TC-EC-S enhanced (p < 0.0001) migration of monocytes compared with TC-S. Both anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (p < 0.0001) TC-EC-S-induced monocyte migration. The modified TC-EC-S (produced in the presence of superoxide dismutase [SOD], dimethyl thiourea [DMTU], or catalase, all scavengers of free radicals) induced lesser monocyte migration than did TC-EC-S alone. CONCLUSIONS: These results suggest that E. coli activates tubular cells to generate cytokines such as MCP-1 and TGF-beta that promote migration of monocytes. Free radicals such as superoxide and hydrogen peroxide may be acting as second messengers in E. coli-induced tubular cell activation.

Antibodies↗
PubMed1998

Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic peptides.

OBJECTIVE AND DESIGN: Extracellular Tat released from HIV-1-infected cells is a mitogenic and motogenic factor for endothelial and Kaposi's sarcoma (KS)-derived cells and is angiogenic in vivo. Here we show for the first time that Tat induces migration of human dendritic cells in a concentration-dependent manner and that the Arg-Gly-Asp (RGD) and basic Tat peptides contribute to dendritic and monocyte cell migration. In vivo, Tat stimulates invasion of macrophages into a matrigel sponge. METHODS: Monocyte and dendritic cell chemotaxis was assessed using the Boyden chamber assay. RESULTS: Tat induced migration of monocyte-derived dendritic cells at the same levels as the N-formyl-Met-Leu-Phe peptide, and of monocytes at levels comparable to RANTES. Peptide mapping of the chemotactic activity of Tat showed that the RGD domain, which has been shown to support integrin-mediated cell migration, and the basic domain which binds and activates the tyrosine kinase receptor KDR on endothelial cells, both had activity. Antibody-blocking experiments indicate that responses to the RGD domain was inhibited by beta1 and alpha vbeta3 integrin blocking antibodies. Combination of the Tat RGD and basic peptides did not show additive effects; however, Tat co-operated with macrophage-chemotactic protein or RANTES in inducing monocyte migration. CONCLUSIONS: Our results show that Tat can act as a chemoattractant for dendritic cells, and that both the RGD and basic domains are involved in this response. These same domains attract monocytes. The alpha vbeta3 and beta1 integrins are equally involved in Tat-induced monocyte migration, while the alpha vbeta3 integrin largely mediates the dendritic cell response to Tat.

Cells, Cultured↗
PubMed2001

Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human monocytes.

Monocyte chemotactic protein 1 (MCP-1)-directed transendothelial migration of monocytes plays a key role in the early development of atherosclerosis. Migration of monocytes requires degradation of extracellular matrices, a process that involves matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP). Recent studies suggest that the alpha1-adrenergic receptor antagonist doxazosin (Dox) might have antiatherosclerotic effects, although the underlying mechanisms are poorly understood. The purpose of the present study was to determine the effects of Dox on MCP-1-directed monocyte migration, MMP-9 activity, and TIMP-1 expression. MCP-1 (50 ng/ml) stimulated migration of human peripheral blood monocytes (HPBM) 2.7+/-0.42-fold and THP-1 human monocytes 5.9+/-0.83-fold compared with unstimulated control. Dox inhibited MCP-1-induced migration in a dose-dependent manner, with a maximal reduction at 10 microM of 69.5+/-5.9% in HPBM and 72.2+/-3.2% in THP-1 cells. Dox blocked migration even after pretreatment with phenoxybenzamine, an irreversible alpha1-adrenergic receptor antagonist (HPBM: phenoxybenzamine 1 microM + Dox 10 microM, 71.9+/-2.2% inhibition; THP-1 cells: phenoxybenzamine 1 microM + Dox 10 microM: 78+/-7.7% inhibition), suggesting that the antimigratory activity of Dox is mediated through a novel mechanism unrelated to its blocking of the alpha1-adrenergic receptor. Dox (10 microM) inhibited MMP-9 activity by 67.6+/-10.5%, whereas MMP-9 protein levels were not affected. Also, Dox increased PMA-induced-tissue inhibitor of MMPs-1 (TIMP-1) expression by 134.4+/-6.6%. Dox 10 microM. The present study demonstrates a potential novel antiatherosclerotic action of Dox by blocking MCP-1-directed monocyte migration, which might be partly mediated by inhibition of MMP-9 activity.

Adrenergic alpha-Antagonists↗
PubMed1990

Enhancement of the antibody-dependent tumoricidal activity of human monocytes by human monocytic colony-stimulating factor.

Human monocytic colony-stimulating factor (hM-CSF) stimulates mature cells as well as progenitor cells of human monocyte lineage. In the present study, we investigated the effect of completely purified native hM-CSF on the tumoricidal activity of human monocytes against Raji (Burkitt lymphoma-derived cell line) using a chromium release assay. Preincubation of human peripheral blood monocytes with hM-CSF for 48 h markedly enhanced their antibody-dependent cellular cytotoxicity (ADCC). This enhancing effect was dependent on the concentration of hM-CSF, and maximal enhancement was achieved at the concentration of 66 ng/ml. The number of receptor sites on monocytes against the Fc portion of immunoglobulin G increased 2- to 4-fold during 48 h incubation with hM-CSF. These results suggest that hM-CSF stimulates monocyte-ADCC by increasing the number of Fc receptor sites on human monocytes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

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

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

Binding Sites, Antibody↗
PubMed1984

Role of specific antibody in interaction of leptospires with human monocytes and monocyte-derived macrophages.

It has previously been shown that human neutrophils ingest and kill nonpathogenic Leptospira biflexa in the absence of serum but that pathogenic Leptospira interrogans is not ingested by neutrophils even in the presence of normal serum. We extended this study by examining the interactions of human monocytes and monocyte-derived macrophages with pathogenic L. interrogans (serovar icterohaemorrhagiae) and evaluating the opsonizing effect of serotype-specific immune serum on the phagocytosis of pathogenic leptospires by monocytes and neutrophils. Leptospires were incubated with monocytes in pellets at 37 degrees C in 5% CO2. No ingestion or killing of pathogenic leptospires occurred when 10% normal serum was used. However, when the pathogenic leptospires were pretreated with serotype-specific immune serum, monocytes or neutrophils in pellets ingested 96% of the organisms and killed 94% of those ingested. Microscopic observations of the interaction confirmed that phagocytosis of the opsonized pathogenic leptospires by monocytes, monocyte-derived macrophages, and neutrophils had occurred. The opsonizing effect of specific antibody may play an important role in the mechanism of host defense against leptospirosis.

Antibodies, Bacterial↗
PubMed1996

H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium avium-M. intracellulare within cultured human monocytes.

Mycobacterium avium-M. intracellulare, an intracellular parasite of mononuclear phagocytes, rarely causes disease in immunocompetent individuals. In contrast, in human immunodeficiency virus type 1-infected patients, M. avium-M. intracellulare can infect almost every tissue and organ. This suggests that immunocompetent individuals have a protective mechanism to control or prevent the infection. How mycobacterial may be killed by the host immune response is unclear. We have recently reported that induction of apoptosis of Mycobacterium bovis BCG-infected macrophages with ATP4- was associated with killing of the intracellular mycobacteria. In the present study, a long-term culture of M. avium-M. intracellulare-infected monocytes was used to further evaluate the interaction between M. avium-M. intracellulare and primary human monocytes. In our system, M. avium-M. intracellulare parasitized the human monocytes and appeared to replicate slowly over 14 days within the host cells. To examine the role of apoptotic mechanisms in survival or death of intracellular mycobacteria, M. avium-M. intracellulare-infected human monocytes were treated with a monoclonal antibody to Fas receptor (APO-1/CD95) or with various concentrations of H2O2. Although both of these exogenous agents induced monocyte apoptosis, optimal killing (65% reduction in CFU) of intracellular M. avium-M. intracellulare was observed only when M. avium-M. intracellulare-infected cells were treated with 10 mM H2O2. Fas-induced apoptosis did not affect M. avium-M. intracellulare viability. Our results suggest that not all stimuli of monocyte apoptosis induce killing of intracellular M. avium-M. intracellulare. Since release of H2O2 following phagocytosis of mycobacteria has been documented, H2O2-induced apoptotic death of M. avium-M. intracellulare-infected monocytes and its association with killing of the intracellular bacilli may be a physiological mechanism of host defense against M. avium-M. intracellulare.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Small (CD14+/CD16+) monocytes and regular monocytes in human blood.

Compared to the obvious phenotypic and functional heterogeneity of tissue macrophages, little information is available on subsets of blood monocytes. We have employed two-color immunofluorescence and flow cytometry for the definition of regular and small monocytes, the latter characterized by the low-density expression of CD14 and the strong expression of the CD16 (Fcy-RIII) antigen. These cells comprise 15% of the blood monocytes and they appear to be similar in phenotype to the alveolar macrophage. The CD14+/CD16+ small monocytes can perform phagocytosis and they produce reactive oxygen, while their capacity for cytokine production is strongly reduced when compared to regular monocytes. At this point it is still unclear as to whether the CD14+/CD16+ small monocytes comprise a specific level of activation or differentiation or a distinct sublineage of human blood monocytes.

Antigens, CD↗
PubMed1997

Characterization of Fc epsilonRI expressing human monocytic cell lines. 1. The role of CD45 on signal transduction in primary monocytes and cell lines.

BACKGROUND: Recently, the high affinity receptor for IgE (Fc epsilonRI), which plays a major role in allergies, has been identified on a number of different antigen-presenting cell types, including human monocytes from atopic and nonatopic donors. In this report human monocytic cell lines were used to test for the expression of Fc epsilonRI, reasoning that a monocytic cell line expressing Fc epsilonRI constitutively would be a useful tool for large scale studies on the regulation of IgE binding and signal transduction. METHODS: Reverse transduction polymerase chain reaction was applied to identify Fc epsilonRI alpha-chain message, flow cytometry to detect Fc epsilonRI surface expression and signal transduction on the cell lines generated by transfection. RESULTS: We report the establishment of monocytic cell lines constitutively expressing Fc epsilonRI (THP1-alpha01 to THP1-alpha40) generated by transfection of the cell line THP1 with a plasmid encoding the Fc epsilonRI alpha-chain only. Fc epsilonRI on the THP1-alpha lines specifically binds IgE and is functional with regard to ligand binding and signal transduction. Comparative studies between the transfectants and primary human monocytes from nonatopic donors demonstrated the regulatory role of the tyrosine phosphatase CD45 on Fc epsilonRI-mediated cell activation. CONCLUSIONS: Monocytic cell lines carry Fc epsilonRI alpha-chain RNA and enhancement by transfection results in surface Fc epsilonRI expression on THP1. Triggering the receptor on the THP1-alpha lines or on human monocytes, which express native Fc epsilonRI, elicits a rapid and transient calcium mobilization, prevented by co-cross-linking of Fc epsilonRI and CD45.

Calcium↗
PubMed1998

Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma LDL.

The subendothelial accumulation of macrophage-derived foam cells is one of the hallmarks of atherosclerosis. The recruitment of monocytes to the intima requires the interaction of locally produced chemokines with specific cell surface receptors, including the receptor (CCR2) for monocyte chemoattractant protein-1 (MCP-1). We have previously reported that monocyte CCR2 gene expression and function are effectively downregulated by proinflammatory cytokines. In this study we identified low density lipoprotein (LDL) as a positive regulator of CCR2 expression. Monocyte CCR2 expression was dramatically increased in hypercholesterolemic patients compared with normocholesterolemic controls. Similarly, incubation of human THP-1 monocytes with LDL induced a rapid increase in CCR2 mRNA and protein. By 24 hours the number of cell surface receptors was doubled, causing a 3-fold increase in the chemotactic response to MCP-1. The increase in CCR2 expression and chemotaxis was promoted by native LDL but not by oxidized LDL. Oxidized LDL rapidly downregulated CCR2 expression, whereas reductively methylated LDL, which does not bind to the LDL receptor, had only modest effects on CCR2 expression. A neutralizing anti-LDL receptor antibody prevented the effect of LDL, suggesting that binding and internalization of LDL were essential for CCR2 upregulation. The induction of CCR2 expression appeared to be mediated by LDL-derived cholesterol, because cells treated with free cholesterol also showed increased CCR2 expression. These data suggest that elevated plasma LDL levels in conditions such as hypercholesterolemia enhance monocyte CCR2 expression and chemotactic response and potentially contribute to increased monocyte recruitment to the vessel wall in chronic inflammation and atherogenesis.

Aged↗
PubMed2004

C-reactive protein promotes monocyte chemoattractant protein-1--mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes.

BACKGROUND: Inflammation plays a crucial role in atherosclerosis. An elevated serum C-reactive protein (CRP) level is a strong marker for future atherosclerotic cardiovascular diseases. In addition, recent data suggest that CRP may directly promote atherogenesis. In this study, we investigated whether CRP can directly activate human circulating monocytes. METHODS AND RESULTS: Incubation of THP-1 monocytes with CRP (10 microg/mL) increased CC chemokine receptor 2 (CCR2) expression at both the protein and transcript levels, which in turn enhanced chemotaxis mediated by monocyte chemoattractant protein-1 (MCP-1) up to 2-fold. The CRP-induced upregulation of CCR2 expression involved binding of CRP to the FcgammaR, most notably FcgammaRI, and phospholipase D1 activation. Serum high-sensitivity CRP levels in 52 normocholesterolemic human subjects were positively correlated with CCR2 surface expression on circulating monocytes (r=0.62, P<0.001) and MCP-1-mediated monocyte chemotaxis (r=0.53, P<0.001). CONCLUSIONS: Elevated blood CRP levels may promote accumulation of monocytes in the atherogenic arterial wall by increasing chemotactic activities of monocytes in response to MCP-1.

Arteriosclerosis↗
PubMed1999

Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration.

To identify the mechanisms that cause monocyte localization in infarcted myocardium, we studied the impact of ischemia-reperfusion injury on the surface expression and function of the monocyte fibronectin (FN) receptor VLA-5 (alpha(5)beta(1) integrin, CD49e/CD29). Myocardial infarction was associated with the release of FN fragments into cardiac extracellular fluids. Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments. Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin. We postulated that changes in VLA-5 expression, which were induced by interactions with cell-binding FN fragments, may alter monocyte migration into tissue FN, a prominent component of the cardiac extracellular matrix. Support for this hypothesis came from experiments showing that FN120 treatment significantly reduced both spontaneous and MCP-1-induced monocyte migration on an FN-impregnated collagen matrix. In vivo, it is likely that contact with cell-binding FN fragments also modulates VLA-5/FN adhesive interactions, and this causes monocytes to accumulate at sites where the fragment concentration is sufficient to ensure proteolytic degradation of VLA-5.

Amino Acid Sequence↗
PubMed2002

Postprandial lipemia is associated with platelet and monocyte activation and increased monocyte cytokine expression in normolipemic men.

The activation of platelets and monocytes has been implicated in the development of cardiovascular diseases. We asked the question if postprandial lipemia following a fat- containing meal is associated with platelet and monocyte activation and increased platelet-monocyte interaction. Thirteen healthy, normal weight, normolipemic males, 20 to 49 years, consumed a 40% fat meal of whole foods. Blood samples were obtained at fasting and 3 1/2 and 6 hours after ingestion. Triglyceride levels increased to 48% over baseline at 3 1/2 hours postconsumption and returned to fasting levels by 6 hours. Multiparameter flow cytometry using monoclonal antibodies showed that the percentage of platelets expressing surface P-selectin and the activated conformation the GPIIb-IIa receptor was significantly higher at 3 1/2 hours compared to fasting. The percentage of platelet-monocyte aggregates increased by 36% at 3 1/2 hours and 43% at 6 hours postconsumption. The percentage of monocytes expressing intracellular tumor necrosis factor-alpha (TNF-alpha) increased seven and eightfold at 3 1/2 and 6 hours, respectively. The expression of interleukin-1beta (IL-1beta increased in a similar manner. These data suggest activation of platelets and monocytes after a moderate fat meal. Repetitive activation of platelets and monocytes could be an early event in the initiation and development of atherosclerosis.

Adult↗
PubMed2004

HCMV activates PI(3)K in monocytes and promotes monocyte motility and transendothelial migration in a PI(3)K-dependent manner.

Human cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised hosts. In immunocompetent hosts, HCMV is associated with chronic inflammatory diseases including atherosclerosis. Monocytes and macrophages are proposed to play key roles in HCMV dissemination to host tissue, and their infection provides a biological link between the lifecycle of HCMV and disease pathology. We hypothesize that viral spread occurs via a mechanism in which infected peripheral blood monocytes, which are nonpermissive for viral replication, extravasate into host tissue and subsequently differentiate into permissive macrophages. Supporting this hypothesis, we recently showed that HCMV specifically induced the differentiation of monocytes into macrophages that become permissive for viral replication. To expand our understanding of HCMV pathogenesis, we next examined monocyte activation and migration, the first events in viral pathogenesis. We show here that HCMV up-regulates phosphatidylinositol 3,4,5 triphosphate kinase [PI(3)K] activity and that this increased PI(3)K activity is essential for infected monocyte-transendothelial migration. This increase in migration occurs through the up-regulation of cell motility in a PI(3)K-dependent process. Last, we show that these activated monocytes express a number of inflammatory mediators via PI(3)K signaling. We propose that the up-regulation of monocyte migration and immune mediators by HCMV infection is required for the hematogenous dissemination of the virus and as a consequence, could promote chronic inflammatory diseases associated with HCMV infection.

Animals↗
PubMed2005

Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-beta 1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes.

Monocyte migration through the disrupted cerebral endothelial cell (EC) junctions plays an essential role in formation of multiple sclerosis (MS) demyelinating lesions. During pathogenesis of MS, activated ECs release endothelial microparticles (EMP), which possibly facilitate transendothelial migration (TEMIG) of monocytes. To assess functional roles of EMP in MS, specifically, their (i) interaction with monocytes, (ii) effect on monocyte TEMIG in an in vitro model of the brain microvascular endothelial cells (BMVEC), (iii) phenotypic profiles of EMP elicited by MS plasma and (iv) the effects of IFN-beta 1b on release of EMP and on TEMIG of monocytes (mono) and monocytes:EMP complexes (mono:EMP) through the BMVEC. The effect of IFN-beta 1b on the release of EMP and the TEMIG of mono and mono:EMP was assessed by preincubating BMVEC cultures of IFN-beta 1b prior to addition of plasma. Three EMP phenotypes, CD54, CD62E and CD31 were assayed. Plasma specimens from 20 patients with relapsing remitting MS (11 in exacerbation, MS-E, and 9 in remission, ME-R) and 10 healthy controls were studied. Incubation of BMVEC with MS-E plasma yielded elevated levels of EMPCD54, EMP62E and EMPCD31 relative to MS-R and control plasmas. MS-E but not MS-R or control plasma also augmented TEMIG of monocytes, respectively. Mono:EMP complexes further augmented TEMIG relative to mono alone, but only in the presence of MS-E plasma; there was no significant effect with MS-R or control plasmas. The presence of IFN-beta 1b inhibited TEMIG of mono and mono:EMP by 20% and 30%, respectively. MS-E but not MS-R plasma elicited release of activation-derived EMP and enhanced TEMIG of mono and mono:EMP. IFN-beta 1b inhibited TEMIG and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism for IFN-beta 1b in MS.

Adjuvants, Immunologic↗
PubMed2003

Dobutamine inhibits monocyte chemoattractant protein-1 production and chemotaxis in human monocytes.

UNLABELLED: It has been reported that, in patients with acute myocardial infarction or congestive heart failure, monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of inflammatory responses and that the level of MCP-1 is correlated with the severity of the disease. We conducted this study to investigate the effects of dobutamine and dopamine on lipopolysaccharide (LPS)-induced MCP-1 production in human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 16 h at 37 degrees C in the presence or absence of dobutamine or dopamine. Enzyme-linked immunosorbent assay was used to examine the effect of dobutamine on MCP-1 synthesis, with the MCP-1 messenger RNA expression examined by reverse transcriptase-polymerase chain reaction. Dobutamine inhibited LPS-induced production of MCP-1, as well as messenger RNA expression, in a dose-dependent manner, whereas dopamine had no significant effect. Furthermore, we demonstrated that dobutamine suppressed MCP-1-induced chemotaxis and peak [Ca(2+)](i) in monocytic THP-1 cells. These findings suggest that dobutamine may modulate monocyte activation, such as chemotaxis and [Ca(2+)](i), as well as MCP-1 production, during therapy for congestive heart failure. IMPLICATIONS: Monocyte chemoattractant protein-1 (MCP-1) plays important roles in the inflammatory processes associated with pathogenesis of cardiovascular diseases. In this study, dobutamine was found to inhibit lipopolysaccharide-induced MCP-1 production and messenger RNA expression, as well as MCP-1-induced chemotaxis and peak [Ca(2+)](i), in human monocytes.

Adrenergic beta-Agonists↗