Endothelial Cells: Role in Infection and Inflammation

McGill, Sandra N.; Ahmed, Najma; Christou, Nicolas V.

doi:10.1007/s002689900366

Cited by 78 publications

(74 citation statements)

References 100 publications

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“…If these EC responses become unbalanced, however, the EC may become pivotal in the development of pathologic processes, such as exaggerated or persistent inflammatory states, vascular diseases, or tumor expansion and metastasis. Additionally, the EC response to stimuli that affect cell survival plays a central role in ischemia/reperfusion injury and in allograft and xenograft injury (1,2). The predominance of cell survival, often measured as protection from apoptosis, may serve to regulate the response to noxious stimuli, so that only severely injured cells are destroyed, as, for example, in inflammation.…”

Section: Ascular Endothelial Cells (Ec)mentioning

confidence: 99%

IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway

Grehan

Levay‐Young

Fogelson

et al. 2005

The Journal of Immunology

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Vascular endothelial cells (EC) perform critical functions that require a balance of cell survival and cell death. EC death by apoptosis and EC activation and injury by the membrane attack complex of complement are important mechanisms in atherosclerosis and organ graft rejection. Although the effects of various cytokines on EC apoptosis have been studied, little is known about their effects on complement-mediated EC injury. Therefore, we studied the abilities of various cytokines to induce protection of porcine aortic EC against apoptosis and killing by human complement, a model of pig-to-human xenotransplantation. We found that porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF-α plus cycloheximide. Maximal protection required 10 ng/ml IL-4 or IL-13, developed progressively from 12 to 72 h of incubation, and lasted 48–72 h after cytokine removal. Protection from complement was not associated with reduced complement activation, C9 binding, or changes in CD59 expression. Inhibition of PI3K prevented development of protection; however, inhibition of p38 MAPK or p42/44 MAPK had no effect. IL-4 and IL-13 induced rapid phosphorylation of Akt. Although protection was inhibited by an Akt inhibitor and a dominant negative Akt mutant transduced into EC, it was induced by transduction of EC with the constitutively active Akt variant, myristylated Akt. We conclude that IL-4 and IL-13 can induce protection of porcine EC against killing by apoptosis and human complement through activation of the PI3K/Akt signaling pathway.

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Section: Ascular Endothelial Cells (Ec)mentioning

confidence: 99%

IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway

Grehan

Levay‐Young

Fogelson

et al. 2005

The Journal of Immunology

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“…Endothelial cells are critical elements in the evolution of inflammation (33,38,47). Through the expression of surface proteins and the secretion of soluble mediators, the endothelium controls vascular tone and permeability, regulates coagulation and thrombosis, and directs the passage of leukocytes into areas of inflammation (33,47).…”

mentioning

confidence: 99%

“…Through the expression of surface proteins and the secretion of soluble mediators, the endothelium controls vascular tone and permeability, regulates coagulation and thrombosis, and directs the passage of leukocytes into areas of inflammation (33,47). In the process of inflammation, endothelial cells are known to produce proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and IL-8 as well as adhesion molecules (33,47). In particular, the chemotactic cytokines (chemokines) and adhesion molecules expressed by endothelial cells are known to be key players in regulating the recruitment of leukocytes to the sites of inflammation (22).…”

mentioning

confidence: 99%

Expression of Chemokine Genes in Human Dermal Microvascular Endothelial Cell Lines Infected withOrientia tsutsugamushi

et al. 2001

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“…T he vascular endothelium plays a vital role in normal physiology and in many pathologic processes (1,2). It regulates vascular tone and blood flow to tissues, controls the transit of molecules and cells through the vessel wall, and maintains an antithrombotic surface to blood flow.…”

mentioning

confidence: 99%

Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement

Black¹,

Grehan²,

Rivard³

et al. 2006

The Journal of Immunology

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Vascular endothelial cells (ECs) can be injured in a variety of pathologic processes that involve activated complement. We reported previously that porcine ECs incubated with exogenous IL-4 or IL-13 are protected from cytotoxicity by human complement and also from apoptosis by TNF-α. The resistance to complement consists of an intrinsic mechanism that is lost a few days after cytokine removal. In our current study, we investigated whether transfer of the IL-4 gene into porcine ECs in vitro and into porcine vascular tissues in vivo would induce efficient and durable protection from human complement. We found that ECs transduced with adenoIL-4 or adenoIL-13 exhibited continuous production of the cytokine and prolonged protection from complement-mediated killing. IL-4 also protected ECs from activation: ECs incubated with IL-4 did not develop cell retraction and intercellular gaps upon stimulation with sublytic complement. The endothelium and subendothelium of pig iliac arteries that were transduced with the IL-4 gene were effectively protected from complement-dependent immediate injury after perfusion with human blood. However, after similar perfusion, the endothelium was immediately lost from arteries that were transduced with a control adenovirus. The protection was not due to up-regulation of the complement regulators decay accelerating factor, membrane cofactor protein, and CD59, or to reduced complement activation, but required the participation of Akt. Although our studies model protection in pig-to-primate xenotransplantation, our findings of IL-4 induction of Akt-mediated protection may be more broadly applicable to EC injury as manifested in ischemia-reperfusion, allotransplantation, and various vascular diseases.

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Endothelial Cells: Role in Infection and Inflammation

Cited by 78 publications

References 100 publications

IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway

IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway

Expression of Chemokine Genes in Human Dermal Microvascular Endothelial Cell Lines Infected withOrientia tsutsugamushi

Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement

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