Monocyte Derivatives Promote Angiogenesis and Myocyte Survival in a Model of Myocardial Infarction

2010 ◽  
Vol 19 (4) ◽  
pp. 369-386 ◽  
Author(s):  
M. Bouchentouf ◽  
P. Paradis ◽  
K. A. Forner ◽  
J. Cuerquis ◽  
M. N. Boivin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Mononuclear Cells ◽  
Endothelial Cell Proliferation ◽  
Blood Monocytes ◽  
Vascular Networks ◽  
Peripheral Blood Mononuclear ◽  
Mature Endothelial Cell ◽  
Tnf Α

In this study, we have investigated the hypothesis that previously reported beneficial effect of peripheral blood mononuclear cells cultured under angiogenic conditions on cardiovascular function following ischemia is not limited to EPCs but also to monocytes contained therein. We first purified and analyzed the phenotype and secretome of human and murine blood monocytes cultured under angiogenic conditions (named MDs for monocyte derivatives) and tested their effect in a mouse model of myocardial infarction (MI). FACS analysis of MDs shows that these cells express mature endothelial cell markers and that their proliferative capacity is virtually absent, consistent with their end-differentiated monocytic ontogeny. MDs secreted significant levels of HGF, IGF-1, MCP-1, and sTNFR-1 relative to their monocyte precursors. MDs were unable to form vascular networks in vitro when cultured on matrix coated flasks. Treatment of murine HL-1 cardiomyocyte cell line with MD-conditioned medium reduced their death induced by TNF-α, staurosporine, and oxidative stress, and this effect was dependent upon MD-derived sTNFR-1, HGF, and IGF-1. We further demonstrate that MD secretome promoted endothelial cell proliferation and capacity to form vessels in vitro and this was dependent upon MD-derived MCP-1, HGF, and IGF-1. Echocardiography analysis showed that MD myocardial implantation improved left ventricle fractional shortening of mouse hearts following MI and was associated with reduced myocardial fibrosis and enhancement of angiogenesis. Transplanted MDs and their secretome participate in preserving functional myocardium after ischemic insult and attenuate pathological remodeling.

INHIBITION OF ENDOTHELIAL CELL PROLIFERATION BY NORMAL HUMAN MONOCYTES

1987 ◽  
Author(s):  
F Liote ◽  
M P Wautier ◽  
E Savariau ◽  
H Setiadi ◽  
J L Wautier
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Umbilical Vein ◽  
Endothelial Cell Proliferation ◽  
Thymidine Uptake ◽  
Blood Monocytes ◽  
Fibronectin Receptor

Human peripheral blood monocytes and macrophages possess factors which are capable of inhibiting or stimulating endothelial cell proliferation. We have further explored if such activity is due to cytotoxic effects of monocytes. Normal mononuclear cells were isolated first by density gradient. Monocytes were then purified by three different techniques: 1) counter centrifugation elutriation (CCE) (Beckman) 2) selective adhesion to gelatin-plasma (GPI) 3) selective adhesion to fibronectin (Fn). Cytotoxicity was estimated by counting the release of 51cr used to label the human umbilical vein endothelial cells (HUVE) prior to the addition of monocytes. Whilst [3H] thymidine incorporation by HUVE permitted us to measure the effect of monocytes on the growth of the endothelial cells. Monocytes were incubated with HUVE (12×103) for 24 to 36h at various concentrations '(1.5-12×103). No cytotoxic effect could be demonstrated but an inhibition of [3h] thymidine uptake was observed and was dependent upon monocytes concentration. Monocytes isolated on GP1 exhibited a significantly higher inhibitory effect (p<0.05) compared to those purified on Fn or by CCE.(GP1: 85±6%, Fn:58±6%, CCE:67±5%). These results indicated t*hat normal monocytes can inhibit endothelial cell proliferation. This activity appeared to be higher when monocytes were isolated on GP1 which suggest that the adhesion on this surface could stimulate monocytes not only by its fibronectin receptor. This inhibitory activity of monocyte on endothelial cells proliferation could be different in patients with vascular disorders.

Characterization of calves exhibiting a novel inheritable TNF-α hyperresponsiveness to endotoxin: associations with increased pathophysiological complications

2005 ◽  
Vol 98 (6) ◽  
pp. 2045-2055 ◽  
Author(s):  
T. H. Elsasser ◽  
J. W. Blum ◽  
S. Kahl
Keyword(s):  
Mononuclear Cells ◽  
Acute Phase Protein ◽  
Peripheral Blood Mononuclear ◽  
Lps Challenge ◽  
Genetic Potential ◽  
Tnf Α ◽  
Related Stress

A subpopulation of calves, herein termed “hyperresponders” (HPR), was identified and defined by the patterns of plasma TNF-α concentrations that developed following two challenges with endotoxin (LPS, 0.8 μg Escherichia coli 055:B5 LPS/kg0.75live body wt) separated by 5 days. The principle characteristic of HPR calves was a failure to develop tolerance to repeated LPS challenge that was evident in the magnitude of the TNF-α concentrations and prolonged severity of pathological sequellae. Whereas calves failing to develop LPS tolerance were identified on the basis of their excessive in vivo plasma TNF-α concentration responses, in vitro TNF-α responses of peripheral blood mononuclear cells isolated from each calf and challenged with LPS or PMA did not correlate or predict the magnitude of in vivo plasma TNF response of the calf. Intentional breeding to obtain calves from bulls and/or cows documented as HPR resulted in offspring displaying the HPR character when similar progeny calves were tested with LPS in vivo, with extensive controls in place to account for sources of variability in the general TNF-α response to LPS that might compromise interpretation of the data. Feed intake, clinical serology and hematology profiles, and acute-phase protein responses of HPR calves following LPS were significantly different from those of calves displaying tolerance. These results suggest that the pattern of plasma TNF-α changes that evolve from a low-level double LPS challenge effectively reveal the presence of a genetic potential for animals to display excessive or prolonged pathological response to LPS-related stress and compromised prognosis for recovery.

scholarly journals Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Youxia Liu ◽  
Hongfen Li ◽  
Huyan Yu ◽  
Fanghao Wang ◽  
Junya Jia ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
B Lymphocytes ◽  
Immune Complexes ◽  
Mononuclear Cells ◽  
Mesangial Cells ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Inflammatory State

Abstract Background The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). Methods This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). Results The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. Conclusions The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

scholarly journals Modulation of TNF-α Secretion in Peripheral Blood Mononuclear Cells by Cocoa Flavanols and Procyanidins

2002 ◽  
Vol 9 (3) ◽  
pp. 135-141 ◽  
Author(s):  
T. K. Mao ◽  
J. van de Water ◽  
C. L. Keen ◽  
H. H. Schmitz ◽  
M. E. Gershwin
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Resting Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Stimulation Of

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammationin vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-α (TNF-α) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used anin vitroculture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-α released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3–4 fold increase in TNF-α relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-α secretion in the range of 48–128% relative to the PHA control. The monomers and dimers were slightly inhibitory (–1.5 and –15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-α levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-α secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.

scholarly journals Soluble ST2 Does Not Regulate TNF-α and IL-6 Production in Dengue Virus-Infected Human Monocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Marisol Pérez-Acosta ◽  
Félix Giovanni Delgado ◽  
Jaime E. Castellanos
Keyword(s):  
Dengue Virus ◽  
Viral Antigen ◽  
Mononuclear Cells ◽  
Acute Infection ◽  
Denv Infection ◽  
Human Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Soluble St2 ◽  
Tnf Α

Dengue virus (DENV) produces an acute infection that results in the overproduction of proinflammatory cytokines. Although increased levels of the immunoregulator soluble ST2 (sST2) protein have been reported in the serum of patients with dengue, its importance during DENV infection remains unclear. The purpose of this study was to evaluate the effect of a recombinant human sST2 protein on the production of TNF-α and IL-6 in an in vitro model of DENV infection. Peripheral blood mononuclear cells (PBMCs) were permissive to in vitro DENV infection since viral antigen was detected in CD14+ monocytes by flow cytometry (median, 1%; range, 0–2.2), and in their supernatants TNF-α and IL-6 were detected. However, sST2 protein was not detected. Using multiple staining on infected PBMC we found that only CD14+ cells produced TNF-α and IL-6. Treatment with human recombinant sST2 protein decreased lipopolysaccharide-induced monocyte TNF-α and IL-6 production. However, this effect was not observed when the monocytes were pretreated with sST2 and later infected with DENV-2. These results suggest that sST2 has different roles in the regulation of TNF-α and IL-6 expression in human monocytes stimulated with LPS and DENV-2.

scholarly journals Acquisition of Hemozoin by Monocytes Down-Regulates Interleukin-12 p40 (IL-12p40) Transcripts and Circulating IL-12p70 through an IL-10-Dependent Mechanism: In Vivo and In Vitro Findings in Severe Malarial Anemia

2006 ◽  
Vol 74 (9) ◽  
pp. 5249-5260 ◽  
Author(s):  
Christopher C. Keller ◽  
Ouma Yamo ◽  
Collins Ouma ◽  
John Michael Ong'echa ◽  
David Ounah ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Severe Malarial Anemia ◽  
Tnf Α ◽  
Malarial Anemia

ABSTRACT Severe malarial anemia (SMA) is a primary cause of morbidity and mortality in immune-naïve infants and young children residing in areas of holoendemic Plasmodium falciparum transmission. Although the immunopathogenesis of SMA is largely undefined, we have previously shown that systemic interleukin-12 (IL-12) production is suppressed during childhood blood-stage malaria. Since IL-10 and tumor necrosis factor alpha (TNF-α) are known to decrease IL-12 synthesis in a number of infectious diseases, altered transcriptional regulation of these inflammatory mediators was investigated as a potential mechanism for IL-12 down-regulation. Ingestion of naturally acquired malarial pigment (hemozoin [PfHz]) by monocytes promoted the overproduction of IL-10 and TNF-α relative to the production of IL-12, which correlated with an enhanced severity of malarial anemia. Experiments with cultured peripheral blood mononuclear cells (PBMC) and CD14+ cells from malaria-naïve donors revealed that physiological concentrations of PfHz suppressed IL-12 and augmented IL-10 and TNF-α by altering the transcriptional kinetics of IL-12p40, IL-10, and TNF-α, respectively. IL-10 neutralizing antibodies, but not TNF-α antibodies, restored PfHz-induced suppression of IL-12. Blockade of IL-10 and the addition of recombinant IL-10 to cultured PBMC from children with SMA confirmed that IL-10 was responsible for malaria-induced suppression of IL-12. Taken together, these results demonstrate that PfHz-induced up-regulation of IL-10 is responsible for the suppression of IL-12 during malaria.

scholarly journals A ComparativeIn VitroStudy of the Effects of Separate and Combined Products ofCitrus e fructibusandCydonia e fructibuson Immunological Parameters of Seasonal Allergic Rhinitis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
E. W. Baars ◽  
M. C. Jong ◽  
I. Boers ◽  
A. F. M. Nierop ◽  
H. F. J. Savelkoul
Keyword(s):  
Allergic Rhinitis ◽  
Seasonal Allergic Rhinitis ◽  
Mononuclear Cells ◽  
Immunological Parameters ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Ifn Γ ◽  
Specific Stimulation

This paper examined the effects of the combined product,Citrus e fructibus/Cydonia e fructibus(Citrus/Cydonia; Citrus and Cydonia: each 0.01 g/mL), and separate products of Citrus (0.01 g/mL) and Cydonia (0.01 g/mL) on the immunological pathways involved in seasonal allergic rhinitis (SAR). Peripheral blood mononuclear cells (PBMCs) from five healthy and five grass pollen-allergic donors were isolated and analyzedin vitroafter polyclonal and allergen-specific stimulation of T cells in the presence of the three extracts. The analyses demonstrated acceptable cell survival with no signs of toxicity. Citrus mainly had a selective effect on reducing allergen-specific chronic inflammatory (TNF-α; Citrus compared to Cydonia and Citrus/Cydonia: −87.4 (P<0.001) and −68.0 (P<0.05), resp.) and Th2 pathway activity (IL-5; Citrus compared to Cydonia: −217.8 (P<0.01); while, both Cydonia and Citrus/Cydonia mainly affected the induction of the allergen-specific Th1 pathway (IFN-γ; Cydonia and Citrus/Cydonia compared to Citrus: 3.8 (P<0.01) and 3.0 (P<0.01), resp.). Citrus and Cydonia demonstrated different working mechanisms in the treatment of SAR and the combination product did not demonstrate larger effects than the separate preparations. Further effectiveness and efficacy studies comparing the effects of the products on SARin vivoare indicated.

scholarly journals CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yulan Ye ◽  
Liping Zhang ◽  
Tong Hu ◽  
Juan Yin ◽  
Lijuan Xu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cell Apoptosis ◽  
Mononuclear Cells ◽  
Circular Rnas ◽  
Infliximab Treatment ◽  
Peripheral Blood Mononuclear ◽  
Novel Approach ◽  
Tnf Α

AbstractIncreasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn’s disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.

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