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At least 991 records · Page 55Linked to original sources
PubMed2006

Platelet-monocyte pro-coagulant interactions in on-pump coronary surgery.

OBJECTIVE: Platelets and monocytes possess haemostatic properties, but the clinical effect of platelet-monocyte interactions on haemostasis following coronary surgery is not known. The study characterises the platelet and monocyte responses in cardiac surgery and its impact on haemostasis. METHODS: In 1342 patients, changes in white blood cell counts (WBC), monocyte counts and platelet counts were measured. PMC formation was analysed by flow-cytometry using monoclonal antibodies against pan-leucocyte marker CD45, monocyte marker CD14 and platelet marker CD42. TF expression was determined using monoclonal antibodies against, CD45, CD14 and human-TF. Continuous variables were expressed as mean+/-SD. Changes in monocyte and platelet counts over time were considered as repeated measures data, and analysed using Generalised Estimating Equations (GEE). Multivariate regression analysis was used to evaluate the effect of several factors on blood loss. RESULTS: A monocytosis occurs with on-pump coronary surgery, but is less pronounced than with off-pump surgery. No difference was seen in patients having redo-surgery or more complex cardiac surgery. Factors associated with monocytosis on multivariate analysis were higher body mass index (p=0.02), diabetes (p=0.035) and smoking (p=0.01). Older patients manifested a lower response (p<0.001). Cross-clamp fibrillation was associated with a lower (p=0.048) monocytic response than was cardioplegia. PMC formation dropped following administration of heparin, peaked at 5 min of CPB, and declined by 2h of CPB (p=0.04). A return towards preoperative levels was found during postoperative days 1-5. No significant change in monocyte TF expression occurred. The mean postoperative blood loss was 581.2+/-292.8 ml, and inversely related to increasing preoperative platelet counts (p<0.001), and to higher monocyte % counts (p=0.012). Patients, who were female (p<0.001), had higher body mass indices (p<0.001), and higher core body temperatures during surgery (p=0.013), as well as patients having perioperative aprotinin (p<0.001) related to less blood loss. CONCLUSIONS: A higher postoperative platelet count as well as monocyte% significantly and independently decreases postoperative blood loss following cardiac surgery.

Aged↗
PubMed2006

SDF-1-induced adhesion of monocytes to vascular endothelium is modulated by azelnidipine via protein kinase C inhibition.

Monocyte-endothelial interaction and its modulation by chemokines play a key role in atherogenesis and inflammation. We examined the potential effects of stromal cell-derived factor (SDF-1) and azelnidipine, a novel dihydropyridine derivative, toward monocyte-endothelial interaction. Human monocytes were prepared from peripheral blood mononuclear cells obtained from healthy volunteers and pretreated with azelnidipine (1 microM) for 48 h, after which their adhesion to interleukin-1beta (IL-1beta)-activated human umbilical vein endothelial cells (HUVECs) was analyzed using an in vitro flow apparatus with a shear stress of 1 dyn/cm(2). In some experiments, monocytes were incubated in the presence of stromal cell-derived factor (SDF-1), a chemokine, just prior to the assay. Pre-incubation of monocytes with SDF-1 enhanced their adhesion to activated HUVECs. When monocytes were pre-incubated in the presence of azelnidipine, baseline levels as well as SDF-1-induced monocyte adhesion levels were reduced. Interestingly, the surface expressions of the adhesion molecules CD11a, CD11b, and CD36, were not changed by azelnidipine treatment. Western blotting analysis revealed that activation of protein kinase C (PKC)alpha was inhibited by azelnidipine treatment, while it also reduced the SDF-1-induced increase in intracellular calcium concentration ([Ca(2+)](i)). Further, pre-incubation of monocytes with Go6976, a potent inhibitor of PKCalpha, significantly reduced monocyte adhesion to HUVECs. Our results demonstrated an inhibitory action of azelnidipine toward adhesive interactions of monocytes to HUVECs, which involves inhibition of PKCalpha and a reduction in [Ca(2+)](i). These findings imply a protective role of azelnidipine against inflammation in atherosclerosis.

Azetidinecarboxylic Acid↗
PubMed2004

Antitumor response of CD14+/CD16+ monocyte subpopulation.

OBJECTIVE: Two main subpopulations of human blood monocytes are distinguished on the basis of CD14 and CD16 expression: the major population with enhanced expression of CD14 (CD14++ monocytes) and the minor one with a weak expression of CD14 coexpressing CD16 (CD14+/CD16+ monocytes). As monocytes and macrophages are involved in antitumor response of the host, we assessed the ability of CD14+/CD16+ monocytes to produce cytokines (intracellular expression, release) and reactive oxygen and nitrogen (ROI, RNI) intermediates following stimulation in vitro with tumor cells. MATERIALS AND METHODS: Monocytes were isolated by elutriation and their subpopulations by FACS sorting. Monocytes and their subpopulations were cocultured with tumor cells. Cytokine (TNF-alpha, IL-12, and IL-10) production was assessed by determination of intracellular protein expression by flow cytometry, and release by ELISA. ROI induction was detected by chemiluminescence and O2- production by flow cytometry, whereas RNI by intracellular expression of inducible NO synthase (iNOS) and nitric oxide (NO) release assessed colorimetrically. RESULTS: CD14+/CD16+ monocytes stimulated with tumor cells showed significantly enhanced production of TNF-alpha, IL-12p40, IL-12p70 (intracellular expression, release), whereas little IL-10 release was observed. CD14+/CD16+ subpopulation did not produce ROI, but showed an increased iNOS expression and NO release. CD14+/CD16+ monocytes also exhibited enhanced cytotoxic and cytostatic activities against tumor cells. CONCLUSIONS: CD14+/CD16+ cells constitute the main subpopulation of blood monocytes involved in antitumor response as judged by enhanced production of proinflammatory cytokines, RNI, and increased cytotoxic/cytostatic activity.

Cell Line, Tumor↗
PubMed2005

Epigallocatechin gallate induces apoptosis of monocytes.

BACKGROUND: Monocytes are the main effector cells of the immune system, and the regulation of their survival and apoptosis is essential for monocyte-involved immune responses. Green tea polyphenol catechin has been reported to have antiallergic and anti-inflammatory activities, but its effect on monocytes has not yet been explored. OBJECTIVE: To elucidate the mechanisms of the anti-inflammatory effect of catechin, we studied the effect of catechin, especially epigallocatechin gallate (EGCG), on the apoptosis of monocytes. METHODS: Isolated peripheral blood monocytes were incubated without or with catechin, and apoptosis was evaluated by annexin V and propidium iodide double-staining or terminal deoxynucleotidyl assay. The activation of caspases 3, 8, and 9 was also evaluated by flow cytometry. The influence of GM-CSF or LPS, the known monocyte survival factors, on the EGCG-induced apoptosis of monocytes was investigated. RESULTS: Among the 4 catechin derivatives tested, EGCG and epicatechin gallate induced apoptosis of monocytes. Caspases 3, 8, and 9, which play a central role in the apoptotic cascade, were dose-dependently activated by EGCG treatment. The EGCG-induced apoptosis of monocytes was not affected by GM-CSF or LPS. CONCLUSION: Catechin, especially EGCG, by promoting monocytic apoptosis, may be a new promising anti-inflammatory agent, and should be tested in clinical trials.

Anti-Inflammatory Agents↗
PubMed2004

Characteristic alteration of monocytes with increased intracellular IL-10 and IL-12 in patients with advanced-stage gastric cancer.

BACKGROUND: It was previously reported that monocytes/macrophages play an important role in mediating T cell dysfunction in tumor-bearing hosts, in which monocytes/macrophages were found to induce the loss of T cell functions concomitantly with induction of defects in T cell signaling molecules. These observations encouraged us to investigate monocytes status in cancer-bearing hosts. MATERIALS AND METHODS: We characterized peripheral blood monocytes in gastric cancer patients with advanced disease (n = 14), in those with early disease (n = 17), and in healthy individuals (n = 14), based on surface marker, oxygen-burst capacity, and intracellular cytokine status (IL-10 and IL-12). RESULTS: Intracellular IL-10 and IL-12 status on monocytes in advanced disease was significantly increased in comparison with those in early disease or healthy individuals, while there were no differences in the surface marker or oxygen-burst capacity of monocytes. To clarify which mediators induced the characteristic differences of monocytes in cancer-bearing hosts, healthy donor-derived monocytes were coincubated with the patient's plasma. The plasma from the patients with advanced disease could induce healthy monocytes to increased intracellular IL-10 and IL-12 status. The phenomenon was significantly inhibited with neutralizing mAbs specific for VEGF. Furthermore, the contents of VEGF in the patient's plasma correlated with their capacity to induce healthy monocytes to increased intracellular IL-10. In addition, the treatment of healthy monocytes with exogenous VEGF resulted in increased intracellular IL-10. CONCLUSIONS: Monocytes in gastric cancer patients with advanced disease showed different characteristics in comparison with those with early disease or healthy individuals, which might be potentially induced by circulating VEGF in the patients.

Antibodies, Monoclonal↗
PubMed2005

17Beta-estradiol inhibits monocyte adhesion via down-regulation of Rac1 GTPase.

Estrogens confer atheroprotective effects that remain poorly understood. We hypothesised that estrogens directly target monocytes, and investigated the pathways via which estrogens might impact on monocyte adhesion. In an in vitro model of the vasculature (parallel plate laminar flow chamber, 2 dynes/cm2), 17beta-estradiol (24 h, 0.1-1 microM) potently inhibits monocyte adhesion. In parallel, 17beta-estradiol down-regulates Rac1 GTPase activity in monocytes. Transfection of monocytic cells with dominant-negative Rac1N17 significantly decreases adhesion to human endothelial cells, while constitutively-active Rac1L61 augments adhesion. As determined by pull-down assays, Rac1 is rapidly activated by the chemokine stromal-derived factor-1 (SDF-1) in human monocytes (100 nM, 30 s). Within the same time period, SDF-1 mediates both ICAM-1/beta2- and VCAM-1/beta1-integrin-dependent monocyte adhesion, which is significantly decreased in cells overexpressing dominant-negative Rac1N17. Inhibitor studies revealed that Rac1-triggered monocyte adhesion is dependent upon actin rearrangement, while production of reactive oxygen species via Rac1 is not involved. Estrogen directly inhibits monocyte adhesion via down-regulation of Rac1, which is both necessary and sufficient to enhance monocyte adhesion under physiological flow conditions. These studies extend current knowledge about the mechanisms responsible for the vascular recruitment of pro-inflammatory cells, and potentially open up new avenues for the therapy of atherosclerosis.

Actins↗
PubMed1998

Cytokine generation capacities of monocytes are reduced in patients with severe heart failure.

BACKGROUND: Immunologic mechanisms mediated by proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Although monocytes are the major source of such cytokines, little is known about their cytokine generation capacities in heart failure. METHODS: We measured plasma levels of 7 major monocyte-related cytokines and the generation capacity of monocytes for 3 cytokines (interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha) on stimulation by lipopolysaccharide in 45 consecutive patients with heart failure and 27 controls. The cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: The generation capacities of monocytes for all 3 cytokines were decreased in patients with worsened outcome during hospitalization and the monocyte capacities were significantly reduced in patients with severe heart failure (New York Heart Association class IV). There was a significant negative correlation between the cytokine generation capacities of monocytes and the plasma cortisol levels. Moreover, cortisol significantly inhibited the cytokine production by lipopolysaccharide-stimulated monocytes ex vivo. CONCLUSIONS: These results indicate that the cytokine generation capacities of monocytes are reduced in patients with severe heart failure, partly because of the negative regulation by cortisol. Because monocytes and cytokines play a central role in immune responses, this reduced monocyte function may be involved in part in the pathophysiology of severe heart failure.

Cytokines↗
PubMed2002

Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and transendothelial migration of monocytes via the protein kinase C pathway.

Inflammatory and immune responses are highly relevant processes in the pathogenesis of atherosclerosis, as illustrated by the central event of monocyte accumulation in atherosclerotic plaques. Integrin LFA-1-mediated adhesion of circulating monocytes to the endothelium is a prerequisite for recruitment of monocytes to these areas. Integrin-mediated adhesion is tightly regulated and integrins are only functional in response to particular monocyte activation stimuli. We investigated the role of oxidized low-density lipoprotein (LDL) in adhesion of resting monocytes prepared by elutriation from endothelium. Our results showed that: (1) oxidized LDL (and MCP-1) induced both LFA-1-mediated adhesion of monocytes to endothelial cells and transendothelial migration of monocytes; (2) oxidized LDL functionally transformed monocyte LFA-1 to an activated form; (3) oxidized LDL induced F-actin polymerization and cytoskeletal rearrangement within seconds; and (4) the LDL-associated antioxidant, alpha-tocopherol, but not beta-tocopherol, inhibited both F-actin polymerization and LFA-1-mediated adhesion of monocytes, which paralleled the effect of protein kinase C (PKC) inhibitors. Our results indicate that oxidized LDL plays a pivotal role in triggering LFA-1 activation and LFA-1-mediated adhesion and transmigration of monocytes to sites of atherosclerotic plaques, via the PKC pathway.

Cell Adhesion↗
PubMed1997

Modification of surface marker expression on CD14 monocytes of allergic patients after lysis or Ficoll purification.

It has been observed that peripheral blood monocytes are often in a primed or activated state in inflammatory diseases such as asthma. However, the majority of these studies have been performed using cells which have been purified by density gradient centrifugation on Percoll or Ficoll-Hypaque. Using cytofluorimetry, we compared the expression of monocyte surface markers of monocytes from untreated blood with monocytes purified by erythrocyte lysis or density centrifugation using the Ficoll technique. Monocytes from two groups of subjects were analyzed: healthy subjects and allergic patients. When compared with untreated blood, the percentage of CD16-positive cells, and the sMFI was significantly greater after monocyte purification (lysis or Ficoll). The expression of CD62L (percentage and sMFI) was modified after monocyte purification. Such modification of these two surface markers was predominantly observed on monocytes from allergic patients, and not on monocytes from healthy subjects. This study suggests that surface marker analysis should be performed on unfractionated whole blood in order to avoid modification of monocyte antigens.

Cell Separation↗
PubMed1980

Monocytic leukemias.

The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

Adult↗
PubMed2001

Monocytes in multiple sclerosis: phenotype and cytokine profile.

Multiple sclerosis (MS) is an inflammatory demyelinating disease characterised by immune abnormalities in the central nervous system (CNS) as well as systemically. Activated, blood-borne monocytes are abundant in MS lesions, the properties of circulating monocytes are incompletely known. To delineate phenotype and levels of cytokine secreting monocytes in MS patients' blood, ELISPOT assays were used for detection and enumeration of monocytes secreting the cytokines IL-6, IL-12, TNF-alpha and IL-10. In parallel, the expression by monocytes of co-stimulatory molecules (CD40, CD80, CD86), major histocompatibility complex molecules (HLA-ABC, HLA-DR) and Fcgamma receptors (CD16, CD64) was examined by flow cytometry. Levels of blood monocytes secreting IL-6 and IL-12 were higher in patients with untreated MS and other neurological diseases (OND) compared to healthy controls, while levels of monocytes secreting TNF-alpha and IL-10 did not differ between groups. MS patients' blood monocytes also displayed elevated mean fluorescence intensity for the co-stimulatory molecule CD86, and MS patients with longer disease duration (>10 years) and higher disease severity (EDSS >3) had higher percentages of CD80 expressing monocytes compared to patients with short duration or lower severity. In conclusion, monocyte aberrations occur in MS and may change over the disease course.

Adult↗
PubMed1997

Prothymosin alpha 1 effects, in vitro, on the antitumor activity and cytokine production of blood monocytes from colorectal tumor patients.

Recent animal studies demonstrate that prothymosin alpha 1 (ProT alpha) enhances the antitumor response by stimulation of mononuclear phagocyte functions. The present study was aimed at characterizing the in vitro effects by ProT alpha on blood monocytes from human colon cancer patients. Purified peripheral blood monocytes were studied in terms of tumor cytostatic ability and cytokine production after incubation with ProT alpha or interferon (rIFN-gamma) and transforming growth factor-beta (TGF beta), used as reference substances. SW620 colon carcinoma cells were used as tumor target cells in growth inhibition experiments. The level of baseline growth inhibitory activity of unstimulated patient's monocytes was significantly lower than that of normal monocytes. The defective antitumor activity of patient monocytes was associated with a higher production of the inhibitory monokines prostaglandin E2 (PGE2) and TGF beta. The stimulation of monocytes by ProT alpha and/or rIFN-gamma elevated the average antitumor activity in all donor groups. The ProT alpha-induced increase was associated with a significantly higher monocytic secretion of IL-1 beta and TNF-alpha. Moreover, the concentrations of TGF beta and PGE2 in the culture supernatants decreased significantly, when patient's monocytes were treated with ProT alpha and/or rIFN-gamma. Additionally, ProT alpha enhanced the diminished antitumor activity of TGF beta-treated normal monocytes. These results suggest that ProT alpha selectively regulates distinct functions of blood monocytes, the effect of this cytokine varying with the parameter and donor population examined. These data provide a rational and biological endpoint for further studies with ProT alpha as an activator of mononuclear function in colon cancer.

Aged↗
PubMed2001

Phenotypic and functional comparison of monocytes from cord blood and granulocyte colony-stimulating factor-mobilized apheresis products.

OBJECTIVE: It is well established that T cells are effector cells in graft-vs-host disease (GVHD), yet the contribution of graft monocytes is less well characterized. Therefore, monocytes in cord blood (CB) and granulocyte colony-stimulating factor-mobilized apheresis products (G-AP), two stem cell grafts associated with reduction of acute and chronic GVHD and relative reduction of acute GVHD, respectively, were compared phenotypically and functionally. MATERIALS AND METHODS: The frequencies, phenotypes, and pinocytosis activities of monocytes from CB and G-AP were determined by flow cytometry and their allostimulatory potential in a primary mixed leukocyte reaction. RESULTS: G-AP contained significantly more monocytes than CB (24.9% +/- 7.1% vs 8.8% +/- 1.5% CD14+ and 62.4 +/- 27.5 x 10(6) vs 0.9 +/- 0.2 x 10(6) CD14+ cells/mL). Monocytes from both sources revealed similar phenotypes. They expressed CD4, CD11a, CD11b, CD11c, CD18, CD32, CD33, CD45R0, CD48, CD50, CD54, CD58, CD64, CD86, CD102, CD116, CD123, and HLA-DR; showed no expression of CD1a and CD83; and weak expression of CD16, CD45RA, and CD80. The levels of CD80 and CD86 expression were comparable; however, in contrast to G-AP monocytes, CB monocytes lacked CD40. There was no difference in pinocytosis activity and allostimulatory capacity of CB and G-AP monocytes. CONCLUSIONS: Monocytes in CB and G-AP are phenotypically and functionally comparable. The only difference observed is the lack of CD40 on CB monocytes.

Antigen Presentation↗
PubMed1999

Oxidative activity of turkey monocytes, following the inoculation with Chlamydia psittaci.

Chemiluminescence (CL) was used to investigate the competence of turkey monocytes to mount a respiratory burst response upon interaction with Chlamydia psittaci. The oxidative activity of purified turkey monocytes, following inoculation with the avian C. psittaci serovar D strain 92/1293, was studied using luminol- and lucigenin-enhanced CL. Purified turkey monocytes were inoculated with C. psittaci at multiplicity of infection (MOI) of approximately 100, 10 and 1. In the presence of luminol, no detectable CL or only a weak CL response was obtained, and if present it increased with increasing MOI. Either sham inoculated monocytes, or monocyte-free control assays supplemented with C. psittaci, gave no detectable luminol-enhanced CL responses. In the lucigenin-enhanced assays, monocytes inoculated with C. psittaci demonstrated an immediate CL peak, the height of which was proportional to the MOI used. Following inoculations at a MOI 1, a faint second peak was observed, when applying high concentrations of lucigenin. Sham inoculated monocytes gave no detectable lucigenin-enhanced CL responses. However, in the presence of lucigenin, the addition of C psittaci to monocyte-free controls also resulted in an immediate CL peak, though no second peak was detected. This immediate lucigenin-dependent CL peak induced by C. psittaci was similar to the one observed in the presence of monocytes, and was not inhibited by superoxide dismutase. We demonstrated that this avian C. psittaci strain induces only a very weak respiratory burst response in turkey monocytes. In contrast, C. psittaci itself elicited an intense non-superoxide mediated lucigenin-dependent CL, indicating that in chlamydial research the detection of superoxide, using lucigenin, should be confirmed with a specific superoxide inhibitor.

Acridines↗
PubMed1996

Interleukin-1 beta and tumor necrosis factor-alpha production by human monocytes cultured with L-thyroxine and thyrocalcitonin: relation to severe root shortening.

The objectives of this study were to determine whether L-thyroxine (T4) and thyrocalcitonin (TCA) influence monocyte production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and to examine IL-1 beta and TNF-alpha production in monocytes from a group of orthodontic patients with severe root shortening. Human monocytes were incubated with varying concentrations of T4 and TCA for 24 hours, and IL-1 beta and TNF-alpha levels were measured by ELISA. At a concentration of 0.1 microgram/ml, T4 and TCA induced significantly more IL-1 beta than untreated controls, and T4 induced more IL-1 beta than TCA. Neither hormone induced significant TNF-alpha release, conversely, TCA had an inhibitory effect on unstimulated monocyte release of TNF-alpha. TCA was also shown to inhibit, but not reverse, the activational effect of lipopolysaccharide on monocyte TNF-alpha release. T4 and TCA concentrations as low as 0.1 pg/ml caused monocytes to release significant amounts of IL-1 beta. The highest concentration of T4 tested (1.0 microgram/ml) induced significantly less IL-1 beta production than lower concentrations. T4- and TCA-treated monocytes bound more labeled IL-1 beta than untreated controls, which suggests that these hormones increase IL-1 receptor expression. There was a wide range of unstimulated and stimulated IL-1 beta and TNF-alpha production by root resorption subject monocytes with no significant differences between resorption and nonresorption group means. This data suggest that patient monocytes did not differ from control monocytes in regard to these cytokine parameters, and therefore in vitro IL-1 beta and TNF-alpha levels could not distinguish resorption subjects.

Adult↗
PubMedDate not supplied

Monocyte adhesion in diabetic angiopathy: effects of free-radical scavenging.

Increased interaction of monocytes with vascular cells is linked to the development and progression of atherosclerosis in patients with diabetes. One major determinant of increased monocyte binding to vascular cells could be oxidative stress. Given the free-radical scavenging properties of gliclazide, we evaluated the ex vivo and in vitro effects of this drug on human monocyte binding to endothelial cells and smooth muscle cells (SMCs). Short-term administration of gliclazide to patients with type 2 diabetes decreases plasma lipid peroxides and lowers the enhanced adhesion of diabetic monocytes to cultured endothelial cells observed before gliclazide treatment. Gliclazide (10 microg/ml) also reduces oxidized low-density lipoprotein (oxLDL)- and advanced glycation end product (AGE)-induced monocyte adhesion to cultured endothelial cells. The suppressive effect of gliclazide on AGE-induced monocyte adhesion to endothelium involves a reduction of cell adhesion molecule mRNA and protein expression and an inhibition of NF-kappaB activation. Gliclazide also inhibits oxLDL-induced monocyte adhesion to cultured human aortic smooth muscle cells (HASMCs). Furthermore, treatment of HASMCs with gliclazide results in a marked decrease in oxLDL-induced monocyte chemoattractant protein-1 expression, both at the gene and protein levels. These results suggest that gliclazide, at concentrations in the therapeutic range (5-10 microg/ml), by its ability to decrease monocyte-vascular cell interactions could reduce monocyte accumulation in the atherosclerotic plaque and thereby contribute to attenuate the sustained inflammatory process that occurs in the vessel wall. These findings suggest that treatment of diabetic patients with gliclazide may prevent or retard the development of vascular disturbances associated with diabetes.

Aged↗
PubMed2003

Role of monocytes and eosinophils in human respiratory syncytial virus infection in vitro.

RSV infection in airway epithelial cells (EC) results in production of the chemokines RANTES and MIP1alpha and the leukocyte differentiation factor GM-CSF. The chemokines attract monocytes and eosinophils to the site of infection, where GM-CSF may influence their function and differentiation. In turn, these inflammatory cells may limit the progression of RSV infection, as well as initiate immune responses. In the present study, the effect of monocytes and eosinophils on viral replication and infection-dependent release of EC-derived cytokines was investigated. The modulation of immune cell costimulatory molecules, CD80, CD86, CD40, and HLA-DR, and the release of the CD4(+) T cell chemoattractant IL-16 were also investigated. Employing immunofluorescence techniques, monocytes and eosinophils in cocultures with infected EC were found to inhibit the spread of RSV to uninfected cells. Monocytes also had a significant effect on replication of RSV. Monocytes phagocytized the virus, while eosinophils inhibited reinfection mainly by extracellular means. The release of G-CSF and GM-CSF in the infected cultures was not significantly affected by either monocytes or eosinophils, while RANTES release was significantly decreased. The expression of CD40, CD80, CD86, and HLA-DR on monocytes, but not on eosinophils, increased in an RSV-dose-dependent manner. IL-16 release was not induced in RSV-infected EC, but was significantly increased in coculture with monocytes. These results suggest that both monocytes and eosinophils attracted to the site of RSV infection play an important role in confining infection, while RSV-exposed monocytes may be involved in promoting/polarizing immune responses to RSV.

Antigens, CD↗
PubMed1997

Activation of human monocytes for enhanced production of interleukin 8 during transendothelial migration in vitro.

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synergistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1 beta. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-alpha, IL-1 beta, or tumor necrosis factor alpha, while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.

Antibodies, Monoclonal↗