Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs

Andonegui, Graciela; Bonder, Claudine S.; Green, Francis; Mullaly, Sarah C.; Zbytnuik, Lori; Raharjo, Eko; Kubes, Paul

doi:10.1172/jci16510c1

Cited by 75 publications

(96 citation statements)

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“…However, more recently, evidence has started to accumulate that indicates that expression of PRRs on the surface of non-immune cells, including VECs, plays an important role in the innate immune response. For example, the accumulation of neutrophils may depend on TLR4 expressed on the surface of VECs, rather than leucocytes, as sequestration of neutrophils in the lung is deeply impaired in mice that lack expression of TLR4 in the endothelium 97. However, the latter observation contrasts with the significant decrease in leucocyte binding caused by lipopolysaccharide (LPS) in HIMECs.…”

Section: Microvascular Endotheliummentioning

confidence: 99%

Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: 'brothers in arms'

Danese

2011

Gut

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Section: Microvascular Endotheliummentioning

confidence: 99%

Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: 'brothers in arms'

Danese

2011

Gut

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“…In a model of sepsis-induced ARDS, antibodies to E-selectin and L-selectin did not affect PMN sequestration [19]. Deficiency in either E-selectin and P-selectin or CD18 alone did not affect sequestration [20]. However, blocking CD18, α 4 , and α 5 integrin in combination resulted in a significant attenuation of fMLP-induced sequestration into the lung.…”

Section: Sequestration Of Neutrophils In the Inflamed Lungmentioning

confidence: 99%

“…Intratracheal instillation of LPS leads to a CD18 dependent recruitment into the alveolar airspace [30]. However, the same endotoxin given intraperitoneally [20] results in a neutrophil sequestration that is independent of CD18 and attenuates PMN recruitment in response to intratracheal LPS [31]. …”

Section: Role Of Adhesion Moleculesmentioning

confidence: 99%

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Untitled

2004

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453 ALI = acute lung injury; ARDS = acute respiratory distress syndrome; BAL = bronchoalveolar lavage; CXCL = CXC chemokine ligand; CXCR = CXC chemokine receptor; ENA = epithelial neutrophil-activating peptide; fMLP = N-formylmethionyl-leucyl-phenylalanine; GAG = glycosaminoglycan; ICAM = intercellular adhesion molecule; IL = interleukin; KC = keratinocyte-derived chemokine; LPS = lipopolysaccharide; MIP = macrophage inflammatory protein; PECAM = platelet endothelial cell adhesion molecule; PMN = polymorphonuclear leukocyte; TF = tissue factor; TFPI = tissue factor pathway inhibitor; TNF = tumor necrosis factor; VCAM = vascular cell adhesion molecule.Available online http://ccforum.com/content/8/6/453 IntroductionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by increased permeability of the alveolar-capillary barrier, resulting in influx of proteinrich edema fluid and consequently impairment in arterial oxygenation. Although mortality has decreased over recent decades, it remains high (30-40%), and pulmonary and nonpulmonary morbidity in ARDS survivors is significant [1]. Although ALI has been described in neutropenic patients, activation and transmigration of circulating neutrophils (polymorphonuclear leukocytes [PMNs]) are thought to play a major role in the early development of ALI [2]. In most animal models, elimination of PMNs markedly decreases the severity of ALI [3]. In addition, recovery from neutropenia in some patients with lung injury is associated with a deterioration in pulmonary function [4].Various animal models have been developed to study the molecular basis of PMN trafficking in the lung (Table 1), but each mimics only some aspects of the clinical situation. Preexisting pulmonary or nonpulmonary diseases, fluid resuscitation, and mechanical ventilation significantly influence the course of ALI but are not considered in most animal models. In addition, experimental methods with which to study PMN recruitment are limited; for example, intravital AbstractAcute lung injury and its more severe form, acute respiratory distress syndrome, are major challenges in critically ill patients. Activation of circulating neutrophils and transmigration into the alveolar airspace are associated with development of acute lung injury, and inhibitors of neutrophil recruitment attenuate lung damage in many experimental models. The molecular mechanisms of neutrophil recruitment in the lung differ fundamentally from those in other tissues. Distinct signals appear to regulate neutrophil passage from the intravascular into the interstitial and alveolar compartments. Entry into the alveolar compartment is under the control of CXC chemokine receptor (CXCR)2 and its ligands (CXC chemokine ligand [CXCL]1-8). The mechanisms that govern neutrophil sequestration into the vascular compartment of the lung involve changes in the actin cytoskeleton and adhesion molecules, including selectins, β 2 integrins and intercellular adhesion molecule-1. The mechanisms of neutrophil entry into the...

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“…We have recently shown that lung inflammation induced following exposure to pig barn air is dependent on the activation of functional TLR4 [13]. Similarly, the role of TLR4 in LPS-induced lung inflammation and neutrophil recruitment in lung microvessels is well established [4,51,52]. Therefore, immunohistochemical expression of NMT and CaN in in the alveolar septa, airway epithelium, and the vascular endothelium in lungs may influence cell signaling leading to expression of IL-8, migration of neutrophils, and lung inflammation.…”

Section: Discussionmentioning

confidence: 99%

EXPRESSION AND ACTIVITIES OFN-MYRISTOYLTRANSFERASE AND CALCINEURIN IN NORMAL AND INFLAMED LUNGS

Charavaryamath

Lemieux

Suri

et al. 2009

Experimental Lung Research

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The role of N-myristoyltransferase and calcineurin is well established in signaling pathways. However, there are no data on their expression and activities in normal and inflamed lungs. The mechanisms of lung inflammation induced following administration of lipopolysaccharides (LPS) or exposure to swine barn air remain unclear. Therefore, we examined expression and activities of N-myristoyltransferase and calcineurin in normal and inflamed lungs of rats. Histopathology showed acute inflammation in the lungs of rats exposed to barn air or LPS but not of control rats. There was no difference in the activities of N-myristoyltransferase and calcineurin among the control, barn-exposed, and LPS-treated rat lungs. Although N-myristoyltransferase and calcineurin were localized in airway epithelium, blood vessel walls, alveolar macrophages, and septa in the lungs of rats from all the groups, the staining intensity was increased in the lungs from rats exposed to intravenous LPS or barn air. Densitometric analyses of Western blots of 55- and 60-kDa polypeptide bands corresponding to N-myristoyltransferase and calcineurin, respectively, in the lung homogenates revealed no differences among the groups. These results show that expression of myristoyltransferase and calcineurin in lung epithelium and endothelium and a cell-specific increase in immunohistochemical expression.

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Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs

Cited by 75 publications

References 0 publications

Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: 'brothers in arms'

Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: 'brothers in arms'

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EXPRESSION AND ACTIVITIES OFN-MYRISTOYLTRANSFERASE AND CALCINEURIN IN NORMAL AND INFLAMED LUNGS

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