Expression and function of endothelial monocyte-activating polypeptide-II in acute lung inflammation

Journeay, W. Shane; Janardhan, Kyathanahalli S.; Singh, Baljit

doi:10.1007/s00011-006-6162-3

Cited by 21 publications

(24 citation statements)

References 23 publications

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“…However excess amounts of mEMAP II delivered in a recombinant form to a murine allograft model of lung development profoundly disrupts not only vascular formation, but strikingly inhibits alveolar growth with a concomitant induction of distal alveolar apoptosis [5]. Furthermore, EMAP II expression is markedly increased in pathologic states associated with lung dysplasia such as in the distal alveoli of infants with Bronchopulmonary dysplasia (BPD) [6], LPS-induced acute lung injury [14], and emphysema [15]. Due to EMAP II's ability to inhibit distal alveoli formation and its elevation in disease processes where ATI cells are compromised, our studies focused on one of the properties associated with the regeneration of gas-exchanging ATI cells, ATII → ATI transdifferentiation.…”

Section: Introductionmentioning

confidence: 99%

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

et al. 2012

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BackgroundDistal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored.MethodIn a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation.ResultsHere, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA.ConclusionOur findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia.

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Section: Introductionmentioning

confidence: 99%

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

et al. 2012

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“…In addition, EMAPII uses the CXCR3 receptor (8), which also binds the chemokines IP-10/CXCL10, I-TAC/CXCL11, MIG/CXCL9, and PF4/CXCL4, leading to the classification of EMAPII as a nonclassical chemokine (8)(9)(10). EMAPII is expressed in the cytosol of all cell types as part of the tRNA-synthetase multienzyme complex (11) and is upregulated by general cellular stress, hypoxia, and LPS (12)(13)(14)(15). EMAPII is secreted from cells as a 43-kDa proform or as 23-and 28-kDa mature forms generated proteolytically by either intracellular (caspase-3, caspase-7) or extracellular proteinases (MMP-9, neutrophil elastase, and cathepsin) (16)(17)(18)(19)(20), many of which are known to participate in the chronic obstructive pulmonary disease (COPD) lung pathobiology (21).…”

Section: Introductionmentioning

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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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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“…Ця пов'язано зі впливом ЕМАР-ІІ на неоваскуляризацію під час ембріогенезу [48]. Його експресія підвищується при експериментальному гострому запаленні легень, що викликане ліпополісахаридом, а інтратрахеальна інсталяція ЕМАР-ІІ приз-водить до міграції моноцитів, лейкоцитів і макрофагів без стимуляції експресії ін-тер лейкіну-1 β та моноцит-активуючого протеїну-2 [49]. Надмірна експресія ЕМАР-ІІ в легенях спричиняє спрощення альвеолярних структур, апоптоз альвеолярних клітин, накопичення макрофагів.…”

Section: участь у розвитку легень під час ембріо-генезу та патогенетиunclassified

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

La¹

2015

Fiziol Zh

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Expression and function of endothelial monocyte-activating polypeptide-II in acute lung inflammation

Abstract: EMAP-II expression is increased in LPS-induced ALI, and that intra-tracheal instillation of mature EMAP-II induces recruitment of monocytes/macrophages and granulocytes into the lungs without stimulating IL-1beta or MIP-2 expression.

Cited by 21 publications

References 23 publications

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

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

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

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