scholarly journals Deficiency of Intercellular Adhesion Molecule 1 Attenuates Microcirculatory Disturbance and Infarction Size in Focal Cerebral Ischemia

1998 ◽  
Vol 18 (12) ◽  
pp. 1336-1345 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Masayasu Matsumoto ◽  
Takuma Mabuchi ◽  
Yoshiki Yagita ◽  
Toshiho Ohtsuki ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Knockout Mice ◽  
Focal Cerebral Ischemia ◽  
Focal Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Transient Focal Ischemia

Recent evidence has shown crucial roles for cell-adhesion molecules in inflammation-induced rolling, adhesion, and accumulation of neutrophils in tissue. Intercellular adhesion molecule-1 (ICAM-1) is one of these adhesion molecules. Previous studies have shown marked reduction in the size of infarction after focal cerebral ischemia by depletion of granulocytes and administration of the antibody against ICAM-1. In the present study we investigated the role of ICAM-1 in the size of ischemic lesions, accumulation of granulocytes, and microcirculatory compromise in focal cerebral ischemia by using ICAM-1–knockout mice. Ischemic lesions were significantly mitigated in knockout mice after permanent and transient focal ischemia, even though the number of granulocytes in the infarcted tissue was almost the same between knockout and wild-type mice. Depletion of granulocytes further decreased the size of ischemic lesions after transient focal ischemia in ICAM-1–knockout mice. Microcirculation was reduced after focal ischemia, but it was better preserved in the cerebral cortex of knockout mice than that of wild-type mice. The present study demonstrated that ICAM-1 played a role in microcirculatory failure and subsequent development and expansion of infarction after focal cerebral ischemia. However, it is highly unlikely that ICAM-1 played a key role in accumulation of granulocytes after focal cerebral ischemia.

scholarly journals Role for Matrix Metalloproteinase 9 after Focal Cerebral Ischemia: Effects of Gene Knockout and Enzyme Inhibition with BB-94

2000 ◽  
Vol 20 (12) ◽  
pp. 1681-1689 ◽  
Author(s):  
Minoru Asahi ◽  
Kazuko Asahi ◽  
Jae-Chang Jung ◽  
Gregory J. del Zoppo ◽  
M. Elizabeth Fini ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Knockout Mice ◽  
Focal Cerebral Ischemia ◽  
Gene Knockout ◽  
Focal Ischemia ◽  
Lesion Size ◽  
Wild Type ◽  
Systemic Hemodynamic ◽  
Ischemic Lesion ◽  
Mmp Inhibitor

It has been shown recently that matrix metalloproteinases (MMPs) are elevated after cerebral ischemia. In the current study, we investigated the pathophysiologic role for MMP-9 (gelatinase B, EC.3.4.24.35) in a mouse model of permanent focal cerebral ischemia, using a combination of genetic and pharmacologic approaches, Zymography and Western blot analysis demonstrated that MMP-9 protein levels were rapidly up-regulated in brain after ischemic onset. Reverse transcription polymerase chain reaction showed increased transcription of MMP-9. There were no differences in systemic hemodynamic parameters and gross cerebrovascular anatomy between wild type mice and mutant mice with a targeted knockout of the MMP-9 gene. After induction of focal ischemia, similar reductions in cerebral blood flow were obtained. In the MMP-9 knockout mice, ischemic lesion volumes were significantly reduced compared with wild type littermates in male and female mice. In normal wild type mice, the broad spectrum MMP inhibitor BB-94 (batimastat) also significantly reduced ischemic lesion size, However, BB-94 had no detectable protective effect when administered to MMP-9 knockout mice subjected to focal cerebral ischemia. These data demonstrate that MMP-9 plays a deleterious role in the development of brain injury after focal ischemia.

scholarly journals Pseudomonas aeruginosa Keratitis in Knockout Mice Deficient in Intercellular Adhesion Molecule 1

1999 ◽  
Vol 67 (2) ◽  
pp. 972-975 ◽  
Author(s):  
Jeffery A. Hobden ◽  
Sharon Masinick-McClellan ◽  
Ronald P. Barrett ◽  
Kenneth S. Bark ◽  
Linda D. Hazlett
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Adhesion Molecule ◽  
Knockout Mice ◽  
Severe Disease ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Disease Response

ABSTRACT In this study, the role of intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of Pseudomonas aeruginosakeratitis was examined by using inbred ICAM-1-deficient knockout mice. These mice had significantly less (P ≤ 0.02) ocular disease than wild-type mice, suggesting that ICAM-1 contributes to a more severe disease response following P. aeruginosainfection.

scholarly journals Mild Hypothermia Attenuates Intercellular Adhesion Molecule-1 Induction via Activation of Extracellular Signal-Regulated Kinase-1/2 in a Focal Cerebral Ischemia Model

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jung Sook Choi ◽  
Jaechan Park ◽  
Kyoungho Suk ◽  
Cheil Moon ◽  
Yong-Ki Park ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Focal Cerebral Ischemia ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Hypothermic Condition

Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium induced by ischemic insult triggers leukocyte infiltration and inflammatory reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral artery occlusion and were kept at 37°C or 33°C during occlusion and rewarmed to normal temperature immediately after reperfusion. Under hypothermic condition, robust activation of extracellular signal-regulated kinase-1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and subsequent attenuation of STAT3 action.

scholarly journals Expression of Tumor Necrosis Factor-Alpha and Intercellular Adhesion Molecule-1 after Focal Cerebral Ischemia in Interleukin-1β Converting Enzyme Deficient Mice

1999 ◽  
Vol 19 (10) ◽  
pp. 1109-1117 ◽  
Author(s):  
Guo-Yuan Yang ◽  
Gerald P. Schielke ◽  
Chao Gong ◽  
Ying Mao ◽  
Hai-Liang Ge ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Ipsilateral Hemisphere ◽  
Ischemic Brain ◽  
Tnf Α ◽  
Factor Alpha

Interleukin-1β (IL-1β) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1β affects ischemic brain are not understood. To investigate the role of IL-1β in regulation of tumor necrosis factor-alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-α and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-α expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1–positive vessels in the ischemic hemisphere was reduced in ICE KO mice ( P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results, The authors' results indicate that TNF-α expression is increased in both ICE KO and wild-type mice suggesting that TNF-α expression is not related to or upregulated by IL-1β. ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1β plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.

scholarly journals Adhesion-dependent interactions between eosinophils and cholinergic nerves

2002 ◽  
Vol 282 (6) ◽  
pp. L1229-L1238 ◽  
Author(s):  
Paul J. Kingham ◽  
W. Graham McLean ◽  
Deborah A. Sawatzky ◽  
Marie Therese Walsh ◽  
Richard W. Costello
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Intercellular Adhesion Molecule ◽  
Cholinergic Nerves ◽  
Intercellular Adhesion Molecule 1 ◽  
Parasympathetic Nerves ◽  
Oxidase Inhibition ◽  
Cell Adhesion Molecule 1 ◽  
Eosinophil Degranulation

Eosinophils adhere to airway cholinergic nerves and influence nerve cell function by releasing granule proteins onto inhibitory neuronal M2 muscarinic receptors. This study investigated the mechanism of eosinophil degranulation by cholinergic nerves. Eosinophils were cocultured with IMR32 cholinergic nerve cells, and eosinophil peroxidase (EPO) or leukotriene C4 (LTC4) release was measured. Coculture of eosinophils with nerves significantly increased EPO and LTC4 release compared with eosinophils alone. IMR32 cells, like parasympathetic nerves, express the adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1). Inhibition of these adhesion molecules alone or in combination significantly inhibited eosinophil degranulation. IMR32 cells also significantly augmented the eosinophil degranulation produced by formyl-Met-Leu-Phe. Eosinophil adhesion to IMR32 cells resulted in an ICAM-1-mediated production of reactive oxygen species via a neuronal NADPH oxidase, inhibition of which significantly inhibited eosinophil degranulation. Additionally, eosinophil adhesion increased the release of ACh from IMR32 cells. These neuroinflammatory cell interactions may be relevant in a variety of inflammatory and neurological conditions.

scholarly journals Distinct Roles For ROCK1 and ROCK2 in the Regulation of Oxldl-Mediated Endothelial Dysfunction

2018 ◽  
Vol 49 (2) ◽  
pp. 565-577 ◽  
Author(s):  
Lei Huang ◽  
Fan Dai ◽  
Lian Tang ◽  
Xiaofeng Bao ◽  
Zhaoguo Liu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Rock Inhibitor ◽  
Vimentin Expression

Background/Aims: This study used Rho-associated protein kinase (ROCK) isoform-selective suppression or a ROCK inhibitor to analyze the roles of ROCK1 and ROCK2 in regulating endothelial dysfunction triggered by oxidized low-density lipoprotein (oxLDL). Methods: ROCK1 or ROCK2 expression in human umbilical vein endothelial cells (HUVECs) was suppressed by small interfering RNA (siRNA). HUVECs were pretreated with 30 μM Y27632 (pan ROCK inhibitor) for 30 min before exposure to 200 μg/mL oxLDL for an additional 24 h. Cell viability was determined by the MTT assay, and cell apoptosis was evaluated by the TUNEL assay. Protein expression and phosphorylation were assessed by Western blot analysis. The morphology of total and phosphorylated vimentin (p-vimentin) and the co-localization of vimentin with vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were detected by the immunofluorescence assay. The adhesion of promonocytic U937 cells to HUVECs was observed by light microscopy. Results: ROCK2 suppression or Y27632 treatment, rather than ROCK1 deletion, effectively reduced endothelial cell apoptosis and preserved cell survival. ROCK2 suppression exhibited improved vimentin and p-vimentin cytoskeleton stability and decreased vimentin cleavage by attenuating caspase-3 activity. In addition, increased p-vimentin expression induced by oxLDL was significantly inhibited by ROCK2 deletion or Y27632 treatment. In contrast, ROCK1 suppression showed no obvious effects on the vimentin cytoskeleton, but significantly regulated the expression of adhesion molecules. Endothelial ICAM-1 or VCAM-1 expression induced by oxLDL was obviously inhibited by ROCK1 suppression or Y27632 treatment. Moreover, the expression of ICAM-1 induced by oxLDL could also be reduced by ROCK2 suppression. Furthermore, ROCK2 deficiency or Y27632 treatment inhibited the redistribution of adhesion molecules and their co-localization with vimentin caused by oxLDL. These effects resulted in the significant inhibition of monocyte-endothelial adhesion induced by oxLDL. Conclusion: The results of this study support the novel concept that ROCK1 is involved in oxLDL-induced cell adhesion by regulating adhesion molecule expression, whereas ROCK2 is required for both endothelial apoptosis and adhesion by regulating both the vimentin cytoskeleton and adhesion molecules. Consequently, ROCK1 and ROCK2 have distinct roles in the regulation of oxLDL-mediated endothelial dysfunction.

Abstract 13301: Methylome-wide Association With Soluble Cell Adhesion Molecules Among Monozygotic Twins

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yan Sun ◽  
Jack Goldberg ◽  
Dean P Jones ◽  
Viola Vaccarino
Keyword(s):  
Cell Adhesion ◽  
Endothelial Function ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Critical Role ◽  
Epigenetic Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Soluble Form ◽  
Intercellular Adhesion Molecule 1

Introduction: Inflammation plays a critical role in the pathogenesis of cardiovascular disease. Epigenetic mechanisms, including DNA methylation (DNAm), is critical in the regulation of inflammatory genes, and can be influenced by inflammation. The soluble form of cell adhesion molecules, including vascular adhesion molecule 1 (sVCAM1), intercellular adhesion molecule 1 (sICAM1), and P-selectin (sP-selectin), are established biomarkers for inflammation and endothelial function, and are linked to cardiovascular events. Methods: To identify epigenetic markers associated with inflammation and endothelial function, we conducted a methylome-wide association study and investigated over 480,000 DNAm sites of peripheral blood cells from 140 monozygotic (MZ) middle-aged male twins from the Emory Twin Study. Results: Using two randomly selected subsets consisting of unrelated subjects, we identified and replicated 69 and 23 DNAm sites significantly associated with sVCAM1, and sICAM1 respectively, adjusted for multiple testing, but none for sP-selectin. All 23 sICAM1-associated DNAm sites were also associated with sVCAM1, including sites on gene ANKRD11 (P=1.51х10-21, 2.62х10-20), KDM2B (P=1.52х10-21, 9.13х10-17), CAPS (P=2.81х10-20, 3.17х10-18), and CUX1 (P=7.63х10-20, 2.84х10-19). They jointly explained 54% and 40% of variance in sVCAM1 and sICAM1 respectively. Two DNAm sites, located on UNC5D and TMEM125, were also significant comparing MZ twins who were phenotypically discordant for both sICAM1 (P=1.79х10-7, 2.78х10-6) and sVCAM1 (P=1.70х10-9, 1.71х10-7). Conclusions: These results suggest that sVCAM1 and sICAM1, but not sP-selectin, may share common pathophysiology in inflammation and endothelial function via an epigenetic mechanism in leukocytes. In addition, the epigenetic association with inflammation may be driven by unshared environmental exposures.

scholarly journals Role of poly(ADP-ribose) synthetase in pulmonary leukocyte recruitment

2003 ◽  
Vol 285 (5) ◽  
pp. L996-L1005 ◽  
Author(s):  
Rainer Kiefmann ◽  
Kai Heckel ◽  
Martina Dörger ◽  
Sonja Schenkat ◽  
Mechthild Stoeckelhuber ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Edema Formation ◽  
Pulmonary Microcirculation

During systemic inflammation, recruitment and activation of leukocytes in the pulmonary microcirculation may result in a potentially life-threatening acute lung injury. We elucidated the role of the poly(ADP-ribose) synthetase (PARS), a nucleotide-polymerizing enzyme, in the regulation of leukocyte recruitment within the lung with regard to the localization in the pulmonary microcirculation and in correlation to hemodynamics in the respective vascular segments and expression of intercellular adhesion molecule 1 during endotoxemia. Inhibition of PARS by 3-aminobenzamide reduced the endotoxin-induced leukocyte recruitment within pulmonary arterioles, capillaries, and venules in rabbits as quantified by in vivo fluorescence microscopy. Microhemodynamics and thus shear rates in all pulmonary microvascular segments remained constant. Simultaneously, inhibition of PARS with 3-aminobenzamide suppressed the endotoxin-induced adhesion molecules expression as demonstrated for intercellular adhesion molecule 1 by immunohistochemistry and Western blot analysis. We confirmed this result with the use of PARS knockout mice. The inhibitory effect of 3-aminobenzamide on leukocyte recruitment was associated with a reduction of pulmonary capillary leakage and edema formation. We first provide evidence that PARS activation mediates the leukocyte sequestration in pulmonary microvessels through upregulation of adhesion molecules. As reactive oxygen species released from leukocyte are supposed to cause an upregulation of adhesion molecules we conclude that PARS inhibition contributes to termination of this vicious cycle and inhibits the inflammatory process.

scholarly journals Comparative Analysis of Luteolin and Luteolin-7-O-Glucoside on anti-Atherogenesis in ApoE Knockout Mice with Hyperhomocysteinemia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yeon-A. Son ◽  
Chung-Mu Park ◽  
Youngsun Song
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecules ◽  
Antioxidative Enzymes ◽  
Adhesion Molecule ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Apoe Knockout Mice ◽  
And Oxidative Stress

AbstractLuteolin is a naturally occurring flavone that reportedly has anti-inflammatory effect. Flavones in plants are usually present in the form of glucosides, although occasionally they are found as aglycones. The bioavailability of flavones may differ when consumed as either aglycones or glucosides. Nonetheless, numerous studies focused on the biological activity of flavonoid aglycones or that in vitro. These findings are supporting reason to compare the anti-atherogenic effect of aglycone and glucoside forms of flavones in vivo. Male ApoE knockout mice (n = 28, 6-week-old) were divided randomly into 4 groups of 7 mice: negative control group, homocysteine control group, luteolin and luteolin7-O-glucoside groups with homocysteine. All animals were fed by a high-fat diet, modified by AIN-93, containing 0.5% of cholesterol and 45% of fat. Luteolin and luteolin-7-O-glycoside were given daily by gavage for 5 weeks (50 mg/kg BW, respectively). To induce hyperhomocysteinemia, homocysteine was provided as a drinking water (0.9g/L). Administration of homocysteine did not affect body weight gain, feed intake and feed efficiency ratio among groups. Homocysteine feeding sharply increased serum concentrations of homocysteine and triglyceride as well as adhesion molecules including monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which were attenuated by the administration of luteolin and luteolin-7-O-glucoside (p < 0.05). Homocysteine administration produced development of atherosclerotic process by the induction of hepatic inducible nitric oxide synthase and cyclooxygenase-2 as well as aortic intercellular adhesion molecule expressions along with diminished expressions of antioxidative enzymes, such as hepatic glutathione reductase (GR), aortic GR and glutathione peroxidase (p < 0.05). Administration of both flavones down-regulated expressions of inflammatory mediators and adhesion molecules as well as up-regulated expressions of antioxidative enzymes (p < 0.05). These data were in accordance with the histopathological observations which were analyzed by hematoxylin and eosin (H&E) stain and immunohistochemistry. In a comparison of both agents, luteolin more potently attenuated inflammation and oxidative stress than luteolin-7-O-glucoside. These results exhibit that luteolin and luteolin-7-O-glycoside ameliorated atherogenic processes through the regulation of inflammation and oxidative stress in ApoE knockout mice with hyperhomocysteinemia. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government of MOE (No 201704340001).

Sign in / Sign up

Export Citation Format

Share Document