scholarly journals Activated macrophages decrease rat cardiac myocyte contractility: importance of ICAM-1-dependent adhesion

1999 ◽  
Vol 277 (1) ◽  
pp. H253-H260 ◽  
Author(s):  
Matthew G. Simms ◽  
Keith R. Walley
Keyword(s):  
Cardiac Myocyte ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Myocardial Dysfunction ◽  
Peritoneal Macrophages ◽  
Intercellular Adhesion Molecule ◽  
Activated Macrophages ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Fractional Shortening

Macrophages are found in the heart as part of the inflammatory response. To determine whether macrophages could contribute to myocardial dysfunction, rat ventricular myocytes were isolated and cocultured with elicited peritoneal macrophages in media containing tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, or endotoxin for 4 h. Cardiac myocytes were electrically stimulated, and fractional shortening was determined using videomicroscopy. When myocytes alone or myocytes in coculture with macrophages separated by a membrane were challenged with TNF-α, lipopolysaccharide, or IL-1, fractional shortening did not decrease. When macrophages were allowed to contact myocytes, fractional shortening decreased from 20.1 ± 0.9% in unchallenged macrophage-myocyte cocultures to 15.5 ± 0.9, 16.3 ± 0.8, and 15.8 ± 0.6% when challenged for 4 h with TNF-α, endotoxin, or IL-1β, respectively ( P < 0.05). Myocytes had a mean adherence of 4.2 ± 0.2 macrophages after TNF-α challenge compared with 2.6 ± 0.3 for controls ( P < 0.05). The number of adherent macrophages was associated with the decrease in fractional shortening. Anti-intercellular adhesion molecule-1 (ICAM-1) reduced macrophage adherence and prevented the decrease in fractional shortening. This decrease was also prevented by desferoxamine, superoxide dismutase, and nitro-l-arginine methyl ester. This suggests that activated macrophages adhere to myocytes via ICAM-1, and adherent macrophages decrease their contractile function via TNF-α, oxygen free radicals, and nitric oxide.

p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction

2005 ◽  
Vol 98 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Hong Kan ◽  
Dale Birkle ◽  
Abnash C. Jain ◽  
Conard Failinger ◽  
Sherry Xie ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cardiac Myocyte ◽  
Kinase Inhibitor ◽  
Ventricular Myocytes ◽  
Myocardial Dysfunction ◽  
P38 Map Kinase ◽  
Border Detection ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Fractional Shortening

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 ± 3.9 vs. 61.9 ± 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 ± 0.8 vs. 12.7 ± 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol ( P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.

Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction

2002 ◽  
Vol 283 (2) ◽  
pp. H650-H657 ◽  
Author(s):  
Christopher D. Raeburn ◽  
Charles A. Dinarello ◽  
Michael A. Zimmerman ◽  
Casey M. Calkins ◽  
Benjamin J. Pomerantz ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Developed Pressure ◽  
Factor Α ◽  
Cell Adhesion Molecule 1

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) have been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a proinflammatory cytokine known to mediate the production of TNF-α and IL-1β and to induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), we hypothesized that neutralization of IL-18 would attenuate lipopolysaccharide (LPS)-induced cardiac dysfunction. Mice (C57BL/6) were injected with LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by 38% at 6 h after LPS. LPS-induced myocardial dysfunction was associated with increased myocardial levels of TNF-α and IL-1β as well as increased expression of ICAM-1/VCAM-1. Pretreatment with neutralizing anti-mouse IL-18 antibody attenuated LPS-induced myocardial dysfunction (by 92%) and was associated with reduced myocardial IL-1β production (65% reduction) and ICAM-1/VCAM-1 expression (50% and 35% reduction, respectively). However, myocardial TNF-α levels were not influenced by neutralization of IL-18. In conclusion, neutralization of IL-18 protects against LPS-induced myocardial dysfunction. IL-18 may mediate endotoxemic myocardial dysfunction through induction of and/or synergy with IL-1β, ICAM-1, and VCAM-1.

Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia

2000 ◽  
Vol 279 (5) ◽  
pp. H2241-H2248 ◽  
Author(s):  
Hiroshi Saito ◽  
Cam Patterson ◽  
Zhaoyong Hu ◽  
Marschall S. Runge ◽  
Ulka Tipnis ◽  
...  
Keyword(s):  
Feedback Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Regulatory Function ◽  
Heart Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Negative Feedback Mechanism ◽  
Proinflammatory Mediators ◽  
Tnf Α

Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1β or TNF-α induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1β. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1β, TNF-α, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1β action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

ICAM-1 and VCAM-1 mediate endotoxemic myocardial dysfunction independent of neutrophil accumulation

2002 ◽  
Vol 283 (2) ◽  
pp. R477-R486 ◽  
Author(s):  
Christopher D. Raeburn ◽  
Casey M. Calkins ◽  
Michael A. Zimmerman ◽  
Yong Song ◽  
Lihua Ao ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cardiac Dysfunction ◽  
Gene Knockout ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Immunofluorescent Staining ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Accumulation

Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in neutrophil-mediated lung and liver injury during sepsis. However, the role of these adhesion molecules as well as the contribution of neutrophils in myocardial dysfunction during sepsis remains to be determined. The purpose of this study was to examine the role of ICAM-1, VCAM-1, and neutrophils in lipopolysaccharide (LPS)-induced myocardial dysfunction. Mice were subjected to LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by nearly 40% at 6 h after LPS. Immunofluorescent staining revealed a temporal increase in myocardial ICAM-1/VCAM-1 expression and neutrophils after LPS. Antibody blockade of VCAM-1 reduced myocardial neutrophil accumulation and abrogated LPS-induced cardiac dysfunction. Antibody blockade or absence of ICAM-1 (gene knockout) also abrogated LPS-induced cardiac dysfunction but did not reduce neutrophil accumulation. Neutrophil depletion (vinblastine or antibody) did not protect from LPS-induced myocardial dysfunction. Our results suggest that although endotoxemic myocardial dysfunction requires both ICAM-1 and VCAM-1, it occurs independent of neutrophil accumulation.

scholarly journals Detection of soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 in the effusion of otitis media with effusion

1995 ◽  
Vol 4 (5) ◽  
pp. 350-354 ◽  
Author(s):  
T. Ganbo ◽  
K.-I. Hisamatsu ◽  
H. Inoue ◽  
K. Kikushima ◽  
A. Mizukoshi ◽  
...  
Keyword(s):  
Otitis Media ◽  
Otitis Media With Effusion ◽  
Interleukin 2 ◽  
Intercellular Adhesion Molecule ◽  
Healthy Controls ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytokine Network ◽  
Tnf Α ◽  
Soluble Interleukin 2 Receptor ◽  
Soluble Intercellular Adhesion Molecule

We measured sIL-2R, TNF-α and sICAM-1 in the sera and middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Although there was no signmcant difference between the sIL-2R levels of the serous and mucoid MEEs, they were significantly higher than serum sIL-2R levels of OME patients and healthy controls. TNF-α levels of the mucoid MEEs were significantly higher than those of the serous type. However, TNF-α was rarely detected in the sera of OME patients or healthy controls. We observed significant differences between the serous and mucoid MEEs with respect to their sICAM-1 levels, which were also higher than serum slCAM-1 levels of OME patients and healthy controls. Our findings suggested that IL-2, TNF-α and ICAM-1 could be significantly involved in the pathogenesis of OME through the cytokine network.

scholarly journals Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF)

2009 ◽  
Vol 116 (10) ◽  
pp. 781-789 ◽  
Author(s):  
Antonio Pinto ◽  
Antonino Tuttolomondo ◽  
Alessandra Casuccio ◽  
Domenico Di Raimondo ◽  
Riccardo Di Sciacca ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Adhesion Molecule ◽  
Plasma Levels ◽  
Characteristic Curve ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Il Interleukin ◽  
Tnf Α

The aim of the present study was to determine the rates of stroke in patients with chronic NVAF (non-valvular atrial fibrillation), evaluating the relationship between plasma levels of inflammatory variables at admission and the occurrence of stroke during a 3-year follow-up. A total of 373 consecutive patients with chronic NVAF were enrolled. Blood samples were drawn within 72 h of admission, and we evaluated plasma levels of IL (interleukin)-1β, TNF-α (tumour necrosis factor-α), IL-6, IL-10, E-selectin, P-selectin, ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and vWF (von Willebrand Factor). Subsequent patient events (stroke at follow-up) were monitored over a 3 year period. By multivariate analysis, only age, hypertension and high levels of IL-6, TNF-α and vWF remained significant predictors of a higher risk of experiencing ischaemic stroke at follow-up. Moreover, plasma values of TNF-α, IL-6 and vWF had a significant area under the ROC (receiver operating characteristic) curve. In conclusion, baseline plasma levels of TNF-α, IL-6 and vWF are predictors of new-onset ischaemic stroke at follow-up in patients with chronic NVAF.

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