Endothelial Cell Determinants of Susceptibility to Neutrophil-Mediated Killing

Murphy, Hedwig S.; Warner, Roscoe L.; Bakopoulos, Natalie; Dame, Michael K.; Varani, James; Ward, Peter A.

doi:10.1097/00024382-199908000-00004

Cited by 31 publications

(19 citation statements)

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“…LPS-stimulated AECs showed enhanced cytotoxicity, implying that neutrophil adherence induces AEC killing. Although several recent studies have shown endothelial cell killing by neutrophils [26,27], the present study suggests susceptibility of epithelial cells to injury related to AEC stimulation by LPS.…”

Section: Discussioncontrasting

confidence: 77%

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Beck‐Schimmer

Madjdpour²,

Kneller³

et al. 2002

European Respiratory Journal

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Intercellular adhesion molecule-1 (ICAM-1) is known to play a central role in lung inflammation. Limited information, however, is available regarding the expression and biological function of ICAM-1 in the alveolar epithelial compartment. The current report analyses the expression pattern of ICAM-1 in primary cultures of rat alveolar epithelial cells (AECs) and in the rat lung following instillation of bacterial endotoxin (lipopolysaccharide (LPS)) in order to better define the role of alveolar epithelial ICAM-1.AECs stimulated in vitro with LPS were evaluated for ICAM-1 and ICAM-1 messenger ribonucleic acid content. Adherence assays with neutrophils and macrophages were performed. Endotoxin-induced ICAM-1 upregulation on AECs was demonstrated in vivo by immunofluorescence staining. In addition, the effect of intratracheally-instilled anti-ICAM-1 was assessed.Significant upregulation of ICAM-1 occurred in vitro and in vivo on AECs after LPS stimulation. Adherence assays showed a 114% increase in adhesion of neutrophils to AECs. Antibody directed against ICAM-1 reduced this adhesion by 40%. A significant reduction in the number of neutrophils in bronchoalveolar lavage fluid and whole lung was seen under airway ICAM-1 blockade.These data indicate that intercellular adhesion molecule-1 participates in the inflammatory response to lipopolysaccharide-induced lung injury in the distal airways by interacting mainly with neutrophils.

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Section: Discussioncontrasting

confidence: 77%

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Beck‐Schimmer

Madjdpour²,

Kneller³

et al. 2002

European Respiratory Journal

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“…NO is known to exert protective effects after I/R by improving blood flow, antagonizing neutrophil activation and adhesion, neutralizing free radical injury, and eliciting antiapoptotic effects (19,23). We have previously shown that supplemental arginine, the substrate for NOS, improves hepatic injury after OLT (34).…”

Section: Discussionmentioning

confidence: 99%

“…NO and citrulline are produced by the family of nitric oxide synthases (NOS) from the substrate L-arginine (32). NO has been shown to exert protective effects in the liver by improving blood flow, antagonizing neutrophil activation and adhesion, neutralizing free radical injury, and eliciting antiapoptotic effects (19,23). The beneficial effects of the L-arginine-NO pathway have also been reported in liver transplantation models.…”

mentioning

confidence: 99%

Liver I/R injury is improved by the arginase inhibitor, N^ω-hydroxy-nor-l-arginine (nor-NOHA)

Reid¹,

Tsung²,

Kaizu³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Liver ischemia-reperfusion (I/R) injury is associated with profound arginine depletion due to arginase release from injured hepatocytes. The purpose of this study was to determine whether arginase inhibition with N -hydroxy-nor-L-arginine (nor-NOHA) would increase circulating arginine levels and decrease hepatic damage during liver I/R injury. The effects of nor-NOHA were initially tested in normal animals to determine in vivo toxicity. In the second series of experiments, orthotopic syngeneic liver transplantation (OLT) was performed after 18 h of cold ischemia time in Lewis rats. Animals were given nor-NOHA (100 mg/kg) or saline before and after graft reperfusion. In normal animals treated with nor-NOHA, there were no histopathological changes to organs, liver enzymes, serum creatinine, or body weight. In the OLT model, animals treated with saline exhibited markedly elevated serum transaminases and circulating arginase protein levels. Nor-NOHA administration blunted the increase in serum arginase activity by 80% and preserved serum arginine levels at 3 h after OLT. Nor-NOHA treatment reduced post-OLT serum liver enzyme release by 50%. Liver histology (degree of necrosis) in nor-NOHA-treated animals was markedly improved compared with the saline-treated group. Furthermore, use of the arginase inhibitor nor-NOHA did not influence polyamine synthesis owing to the decrease in ornithine levels. Arginase blockade represents a potentially novel strategy to combat hepatic I/R injury associated with liver transplantation. liver transplantation; arginine; nitric oxide; preservation injury ISCHEMIA-REPERFUSION (I/R) injury is a pathophysiological process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery to the compromised tissue. Transient episodes of hepatic ischemia occur during solid organ transplantation, trauma, hypovolemic shock, and elective liver resection, when inflow occlusion or total vascular exclusion is used to minimize blood loss. The pathophysiology of liver I/R injury includes both direct cellular damage as the result of the ischemic insult as well as delayed dysfunction and damage resulting from activation of inflammatory pathways (3,6,8,21,26,29). The injury that results from I/R after liver transplantation contributes to primary nonfunction in ϳ5-10% of liver grafts and delayed graft function in 15-30% of cases (9, 30).Nitric oxide (NO) is known to have an important role in regulating liver physiology and blood flow. NO and citrulline are produced by the family of nitric oxide synthases (NOS) from the substrate L-arginine (32). NO has been shown to exert protective effects in the liver by improving blood flow, antagonizing neutrophil activation and adhesion, neutralizing free radical injury, and eliciting antiapoptotic effects (19, 23). The beneficial effects of the L-arginine-NO pathway have also been reported in liver transplantation models. Experiments using arginine supplementation and NO donors have shown that NO serves to improve liver ischemia injury...

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“…Cells grown to confluence in 4 -6 days were trypsinized and used at 90 -95% confluence for all experimental studies (passage 1). Cultured cells were characterized by a cobblestone appearance and specific staining for vWF as well as flow cytometric determination of uptake of 1,1Ј-dioctadexyl-3,3,3Ј,3Ј-tetramethyl-indocrbocynanine perchlorate according to previously described methods (42)(43)(44) 125 I using the chloramine T-based method as previously described (45). This method involves gentle oxidation and preserves the functional (chemotactic) activity of C5a (45).…”

Section: Mdmec Culturementioning

confidence: 99%

Expression and Function of C5a Receptor in Mouse Microvascular Endothelial Cells

Laudes¹,

Chu²,

Huber‐Lang³

et al. 2002

The Journal of Immunology

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110

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The complement-derived anaphylatoxin, C5a, is a potent phlogistic molecule that mediates its effects by binding to C5a receptor (C5aR; CD88). We now demonstrate specific binding of radiolabeled recombinant mouse C5a to mouse dermal microvascular endothelial cells (MDMEC) with a Kd50 of 3.6 nM and to ∼15,000–20,000 receptors/cell. Recombinant mC5a competed effectively with binding of [125I]rmC5a to MDMEC. Enhanced binding of C5a occurred, as well as increased mRNA for C5aR, after in vitro exposure of MDMEC to LPS, IFN-γ, or IL-6 in a time- and dose-dependent manner. By confocal microscopy, C5aR could be detected on surfaces of MDMEC using anti-C5aR Ab. In vitro expression of macrophage inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1) by MDMEC was also measured. Exposure of MDMEC to C5a or IL-6 did not result in changes in MIP-2 or MCP-1 production, but initial exposure of MDMEC to IL-6, followed by exposure to C5a, resulted in significantly enhanced production of MIP-2 and MCP-1 (but not TNF-α and MIP-1α). Although LPS or IFN-γ alone induced some release of MCP-1 and MIP-2, pre-exposure of these monolayers to LPS or IFN-γ, followed by addition of C5a, resulted in synergistic production of MIP-2 and MCP-1. Following i.v. infusion of LPS into mice, up-regulation of C5aR occurred in the capillary endothelium of mouse lung, as determined by immunostaining. These results support the hypothesis that C5aR expression on MDMEC and on the microvascular endothelium of lung can be up-regulated, suggesting that C5a in the co-presence of additional agonists may mediate pro-inflammatory effects of endothelial cells.

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Endothelial Cell Determinants of Susceptibility to Neutrophil-Mediated Killing

Cited by 31 publications

References 0 publications

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Liver I/R injury is improved by the arginase inhibitor, N^ω-hydroxy-nor-l-arginine (nor-NOHA)

Expression and Function of C5a Receptor in Mouse Microvascular Endothelial Cells

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Endothelial Cell Determinants of Susceptibility to Neutrophil-Mediated Killing

Cited by 31 publications

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Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation

Liver I/R injury is improved by the arginase inhibitor, Nω-hydroxy-nor-l-arginine (nor-NOHA)

Expression and Function of C5a Receptor in Mouse Microvascular Endothelial Cells

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Liver I/R injury is improved by the arginase inhibitor, N^ω-hydroxy-nor-l-arginine (nor-NOHA)