A monoclonal rat anti-mouse EMAP II antibody that functionally neutralizes pro- and mature-EMAP II in vitro

Gangaraju, Rajashekhar; Mitnacht-Kraus, Rita; Ispe, Ute; Garrison, Jana; Hou, Yonghao; Taylor, Brian J.; Petrache, Irina; Vestweber, Dietmar; Clauss, Matthias

doi:10.1016/j.jim.2009.08.003

Cited by 9 publications

(12 citation statements)

References 26 publications

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“…The rat monoclonal neutralizing antibody M7/1 against mouse EMAPII was developed by immunizing Lewis rats with recombinant murine pro-EMAPII, as described previously (47). For purification of monoclonal antibodies for in vivo studies, hybridomas were grown in protein-free hybridoma medium (GIBCO-BRL), and antibodies were purified with protein G-Sepharose (Pharmacia).…”

Section: Methodsmentioning

confidence: 99%

“…26). Antibodies (50 μg/application) were administered directly to the lung via inhalation of a nebulized solution, which showed effective deposition in the lung parenchyma at 15 minutes by fluorescence microscopy of the lung and at 4 hours by immune adsorption analysis of recovered biotinylated antibody from plasma (Supplemental Figure 3).…”

Section: Neutralization Of Emapii Levels Markedly Reduces Cs-induced mentioning

confidence: 99%

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Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

et al. 2011

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Pulmonary emphysema is a disease characterized by alveolar cellular loss and inflammation. Recently, excessive apoptosis of structural alveolar cells has emerged as a major mechanism in the development of emphysema. Here, we investigated the proapoptotic and monocyte chemoattractant cytokine endothelial monocyte-activating protein 2 (EMAPII). Lung-specific overexpression of EMAPII in mice caused simplification of alveolar structures, apoptosis, and macrophage accumulation, compared with that in control transgenic mice. Additionally, in a mouse model of cigarette smoke-induced (CS-induced) emphysema, EMAPII levels were significantly increased in murine lungs. This upregulation was necessary for emphysema development, as neutralizing antibodies to EMAPII resulted in reduced alveolar cell apoptosis, inflammation, and emphysema-associated structural changes in alveoli and small airways and improved lung function. The mechanism of EMAPII upregulation involved an apoptosis-dependent feed-forward loop, since caspase-3 instillation in the lung markedly increased EMAPII expression, while caspase inhibition decreased its production, even in transgenic EMAPII mice. These findings may have clinical significance, as both current smokers and exsmoker chronic obstructive pulmonary disease (COPD) patients had increased levels of secreted EMAPII in the bronchoalveolar lavage fluid compared with that of nonsmokers. In conclusion, we suggest that EMAPII perpetuates the mechanism of CS-induced lung emphysema in mice and, given its secretory nature, is a suitable target for neutralization antibody therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Neutralization Of Emapii Levels Markedly Reduces Cs-induced mentioning

confidence: 99%

Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

et al. 2011

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“…p38 MAPK inhibitor (SB203580) was purchased from Sigma. Recombinant EMAP II and monoclonal neutralizing antibodies to EMAP II were produced and purified as recently described (34,37). Adult human lung microvascular endothelial cells (HLMVEC; Clonetics, Lonza) were cultured in EGM2MV media.…”

Section: Reagents and Cellsmentioning

confidence: 99%

“…Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL Apoptosis Detection Kit; Millipore) in attached endothelial cells as previously described (37). Briefly, images were analyzed by MetaMorph image software, and results were expressed by computing the ratios between TUNEL-positive and total (DAPI positive) cells.…”

Section: Reagents and Cellsmentioning

confidence: 99%

HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3

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et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chronic lung diseases, such as pulmonary emphysema, are increasingly recognized complications of infection with the human immunodeficiency virus (HIV). Emphysema in HIV may occur independent of cigarette smoking, via mechanisms that are poorly understood but may involve lung endothelial cell apoptosis induced by the HIV envelope protein gp120. Recently, we have demonstrated that lung endothelial apoptosis is an important contributor to the development of experimental emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II) in the lung. Here we investigated the role of EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in cell surface expression of EMAP II and its receptor CXCR3. This surface expression occurred via a mechanism involving gp120 signaling through its CXCR4 receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially required for gp120-induced apoptosis and exposures to low gp120 concentrations enhanced the susceptibility of endothelial cells to undergo apoptosis when exposed to soluble cigarette smoke extract. These data indicate a novel mechanism by which HIV infection causes endothelial cell loss involved in lung emphysema formation, independent but potentially synergistic with smoking, and suggest therapeutic targets for emphysema prevention and/or treatment.

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“…Враховуючи патогенетичне значення ЕМАР-ІІ при деяких захворюваннях, були розроблені моноклональні антитіла, здатні як виявляти різні форми цього пептиду, так і нейтралізувати його дію, спрямовану на міграцію моноцитів у периферичній крові людини, ЕМАР-ІІ-індукований апоптоз клітин [72,73].…”

Section: участь у розвитку інших захворюваньunclassified

Endothelial Monocyte-Activating Polypeptide-Ii: Properties, Functions, and Pathogenetic Significance

La¹

2015

Fiziol Zh

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A monoclonal rat anti-mouse EMAP II antibody that functionally neutralizes pro- and mature-EMAP II in vitro

Cited by 9 publications

References 26 publications

Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3

Endothelial Monocyte-Activating Polypeptide-Ii: Properties, Functions, and Pathogenetic Significance

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