Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor

1999 ◽  
Vol 276 (4) ◽  
pp. G1016-G1026 ◽  
Author(s):  
Maria Casadevall ◽  
Esteban Saperas ◽  
Julián Panés ◽  
Azucena Salas ◽  
Donald C. Anderson ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Corticotropin Releasing Factor ◽  
Cell Interactions ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
High Dose ◽  
Intercellular Adhesion Molecule 1 ◽  
Anti Inflammatory

Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not α-melanocyte-stimulating hormone (α-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of α-MSH.

Role of ICAM-1 in chronic hepatic allograft rejection in the rat

2002 ◽  
Vol 283 (1) ◽  
pp. G196-G203 ◽  
Author(s):  
John Wong ◽  
Paul Kubes ◽  
Yikun Zhang ◽  
Yang Li ◽  
Stefan J. Urbanski ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Brown Norway ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Hepatic Allograft

The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10 mg · kg−1· day−1× 6 days ip) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital microscopy. Liver histology, biochemistry, and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared with isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared with control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3 ± 1.2 days) compared with the controls (25.2 ± 2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1 dependent and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.

Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion

2006 ◽  
Vol 291 (2) ◽  
pp. H694-H704 ◽  
Author(s):  
Karyn J. Lister ◽  
Michael J. Hickey
Keyword(s):  
Adhesion Molecule ◽  
Immune Complexes ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion ◽  
Microvascular Permeability ◽  
Intercellular Adhesion Molecule ◽  
Complement Pathway ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Tissues

Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues. However, very few studies have examined the ability of ICs to induce inflammatory responses in the brain. Therefore, using preformed ICs or the reverse passive Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed to investigate the ability of ICs to induce an inflammatory response in the cerebral (pial) microvasculature. Application of preformed ICs immediately increased pial microvascular permeability, with a minimal change in leukocyte adhesion in pial postcapillary venules. In contrast, initiation of the RPA response in the pial microvasculature induced changes in cerebral microvascular permeability and increased leukocyte adhesion in pial postcapillary venules. The RPA response induced deposition of C3 in perivascular regions adjacent to sites of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability and leukocyte adhesion, indicating that the complement pathway was critical for this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC-induced microvascular permeability. However, this did not require intercellular adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1 did not alter RPA-induced microvascular permeability and adhesion. These findings demonstrate that ICs are capable of rapidly inducing inflammatory responses in the cerebral microvasculature, with the complement pathway and leukocyte recruitment playing critical roles in microvascular dysfunction.

Abstract 171: Role of α-Actinin-4-Dependent Endothelial Cell Stiffness in Neutrophil Transmigration

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Peter Hordijk ◽  
Antje Schaefer ◽  
Joost te Riet ◽  
Katje Ritz ◽  
Mark Hoogenboezem ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Feedback Loop ◽  
Leukocyte Adhesion ◽  
Cell Stiffness ◽  
Intercellular Adhesion Molecule ◽  
Ageing Population ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Lining ◽  
Human Disorders

Inflammation is causally linked to many chronic human disorders and constitutes a growing problem in the ageing population. The inflammatory process is driven by interactions of activated leukocytes with the endothelial lining of blood vessels. This requires binding of leukocyte β2-integrins to endothelial ICAM-1 (InterCellular Adhesion Molecule-1), which allows leukocyte adhesion, spreading, crawling and transendothelial migration (TEM). Integrin binding induces ICAM-1 clustering and its consequent association to F-actin which enforces leukocyte adhesion. Here, we analyzed the molecular basis of this positive feedback loop. We show that ICAM-1 clustering promotes its binding to F-actin through distinct complexes with FilaminB, Cortactin and α-Actinin-4. We found that α-Actinin-4 regulates endothelial cell peripheral stiffness, which is sensed by adherent neutrophils and promotes adhesion, spreading, crawling and TEM. Conversely, increasing endothelial cell stiffness stimulates the ICAM-1-α-Actinin-4 interaction. Finally, we found that the endothelial lining of atherosclerotic plaques, which is characterized by increased stiffness and leukocyte infiltration, shows increased expression of α-Actinin-4. These results identify α-Actinin-4-regulated endothelial cell stiffness as a novel pro-inflammatory event that promotes ICAM-1-mediated leukocyte adhesion and TEM.

scholarly journals O-linked β-N-acetylglucosamine During Hyperglycemia Exerts Both Anti-Inflammatory and Pro-Oxidative Properties in the Endothelial System

2009 ◽  
Vol 2 (3) ◽  
pp. 172-175 ◽  
Author(s):  
Angana Gupta Rajapakse ◽  
Xiu-Fen Ming ◽  
João M. Carvas ◽  
Zhihong Yang
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiovascular Complications ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Anti Inflammatory ◽  
Vascular Adhesion

Elevated cellular levels of proteinO-linked β-N-acetylglucosamine (O-GlcNAc) through hexosamine biosynthesis pathway (HBP) are suggested to contribute to cardiovascular adverse effects under chronic hyperglycemic condition associated with oxidative stress and inflammation. Conversely, enhancingO-GlcNAc levels have also been demonstrated being protective against myocardial ischemia/reperfusion injury. We recently demonstrated that hyperglycemia increases oxidative stress and HBP flux in endothelial cells and enhances endothelial expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in response to tumor necrosis factor-α (TNFα) through oxidative stress rather than HBP pathway. Here we present further complementary data showing that enhancingO-GlcNAc levels by glucosamine does not mimic hyperglycemia's effect on TNFα-induced endothelial VCAM-1 and ICAM-1 expression. Glucosamine however inhibits ICAM-1 (not VCAM-1) expression and induces superoxide generation in the cells. The results further suggest that increasedO-GlcNAc levels do not mediate the enhancing effect of hyperglycemia on the endothelial inflammatory responses to TNFα. In contrast, it exerts certain anti-inflammatory effects accompanied by pro-oxidative properties. Further work should delineate the exact role of HPB pathway in different aspects of cardiovascular functions, especially those of diabetic cardiovascular complications.

scholarly journals CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during InflammationIn Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kirsten Buschmann ◽  
Lutz Koch ◽  
Natascha Braach ◽  
Hanna Mueller ◽  
David Frommhold ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Models ◽  
Trauma Model

It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy. Flow chamber experiments, expression analysis, functional depletion, and knockout of key adhesion molecules gave mechanistic insight in involved pathways. We demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose-dependent manner. Notably, during tumor necrosis factor (TNF)α-induced inflammation leukocyte recruitment was not further enhanced by glucose administration, whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model, indicating that proinflammatory properties of glucose are stimulus dependent. Experiments with functional or genetic inhibition of the chemokine receptor CXCR2, intercellular adhesion molecule 1 (ICAM1), and lymphocyte function antigen 1 (LFA1) suggest that keratino-derived-chemokine CXCL1-triggered interactions of ICAM1 and LFA1 are crucially involved in the trauma model of inflammation. The lacking effect of glucose onβ2integrin expression and on leukocyte adhesion in dynamic flow chamber experiments argues against leukocyte-driven underlying mechanisms and favours an endothelial pathway since endothelial ICAM1 expression was significantly upregulated in response to glucose.

scholarly journals Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro

2000 ◽  
Vol 278 (5) ◽  
pp. L1008-L1017 ◽  
Author(s):  
Catherine M. Woods ◽  
Gerald Neslund ◽  
Elisabeth Kornbrust ◽  
Stephen F. Flaim
Keyword(s):  
Acute Lung Injury ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Partial Liquid Ventilation ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Monolayers ◽  
Activated Neutrophils

Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed >40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation ( P < 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung.

Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung

1995 ◽  
Vol 78 (6) ◽  
pp. 2245-2252 ◽  
Author(s):  
T. M. Moore ◽  
P. Khimenko ◽  
W. K. Adkins ◽  
M. Miyasaka ◽  
A. E. Taylor
Keyword(s):  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Ischemia And Reperfusion ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion Molecules ◽  
Permeability Increase ◽  
Isolated Rat Lung

Leukocyte adherence to the endothelium after ischemia and reperfusion contributes to microvascular injury in most organs. The purpose of this study was to evaluate the leukocyte and endothelial cell adhesion molecules involved with ischemia-reperfusion (I/R)-induced pulmonary microvascular injury in the isolated rat lung. After 45 min of ischemia and 30 min of reperfusion, microvascular permeability was significantly increased and lung retention of leukocytes occurred. Pretreatment with monoclonal antibodies against the leukocyte adhesion molecule CD18 or the endothelial cell adhesion molecules intercellular adhesion molecule 1 and P-selectin significantly attenuated the I/R-induced permeability increase and lung sequestration of neutrophils, mononuclear leukocytes, and eosinophils. In contrast, immunoneutralization of the rat leukocyte adhesion molecule L-selectin neither protected against the I/R-induced permeability increase nor prevented lung sequestration of neutrophils and eosinophils. We conclude that leukocyte adherence in the pulmonary, microvasculature and subsequent permeability increase after I/R is dependent on the integrin CD18, its endothelial cell ligand intercellular adhesion molecule 1, and the endothelial cell rolling factor P-selectin but not the leukocyte rolling factor L-selectin.

Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1

2001 ◽  
Vol 280 (2) ◽  
pp. H634-H641 ◽  
Author(s):  
S. Bradley Forlow ◽  
Klaus Ley
Keyword(s):  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Striking Similarity ◽  
Leukocyte Rolling ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Adhesion Efficiency

To study selectin-independent leukocyte recruitment and the role of intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking all three selectins and ICAM-1 (E/P/L/I−/−) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they showed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte firm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycollate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitment was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on α4-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and α4-integrins). A striking similarity of leukocyte adhesion efficiency in E/P/L−/− and E/P/I−/− mice suggests a pathway in which leukocyte rolling through L-selectin requires ICAM-1 for adhesion and recruitment. Comparison of our data with mice lacking individual or other combinations of adhesion molecules reveal that elimination of more adhesion molecules further reduces leukocyte recruitment but the effect is less than additive.

scholarly journals Leukocyte-endothelial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling

2008 ◽  
Vol 295 (3) ◽  
pp. H969-H977 ◽  
Author(s):  
Ronen Sumagin ◽  
Elena Lomakina ◽  
Ingrid H. Sarelius
Keyword(s):  
Endothelial Cell ◽  
Cell Interactions ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Independent Manner ◽  
Solute Permeability ◽  
Tnf Α ◽  
Key Characteristics ◽  
The Relationship ◽  
Dependent Pathway

Two key characteristics of the inflammatory response are the recruitment of leukocytes to inflamed tissue as well as changes in vessel permeability. We explored the relationship between these two processes using intravital confocal microscopy in cremasters of anesthetized (65 mg/kg Nembutal ip) mice. We provide direct evidence that intercellular adhesion molecule-1 (ICAM-1) links leukocyte-endothelial cell interactions and changes in solute permeability ( Ps). Importantly, we show that arterioles, not just venules, respond to proinflammatory stimuli, thus contributing to microvascular exchange. We identified two independent, ICAM-1-mediated pathways regulating Ps. Under control conditions in wild-type (WT) mice, there is a constitutive PKC-dependent pathway ( Ps = 1.0 ± 0.10 and 2.2 ± 0.46 × 10−6 cm/s in arterioles and venules, respectively), which was significantly reduced in ICAM-1 knockout (KO) mice ( Ps = 0.54 ± 0.07 and 0.77 ± 0.11 × 10−6 cm/s). The PKC inhibitor bisindolylmaleimid l (1 μmol/l in 0.01% DMSO) decreased Ps in WT mice to levels similar to those in ICAM-1 KO mice. Likewise, a PKC activator (phorbol-12-myristate-acetate; 1 μmol/l in 0.01% DMSO) successfully restored Ps in ICAM-1 KO vessels to be not different from that of the WT controls. On the other hand, during TNF-α-induced inflammation, Ps in WT mice was significantly increased (2-fold in venules and 2.5-fold in arterioles) in a Src-dependent and PKC-independent manner. The blockade of Src (PP2; 2 μmol/l in 0.01% DMSO) but not PKC significantly reduced the TNF-α-dependent increase in Ps. We conclude that ICAM-1 plays an essential role in the regulation of Ps in microvessels and that there are two separate (constitutive and inducible) signaling pathways that regulate permeability under normal and inflamed conditions.

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