Effects of Lipopolysaccharide and<i>Mannheimia haemolytica</i>Leukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells

McClenahan, David; Hellenbrand, Katrina M.; Atapattu, Dhammika N.; Aulik, Nicole; Carlton, David P.; Kapur, Arvinder; Czuprynski, Charles J.

doi:10.1128/cvi.00344-07

Cited by 34 publications

(25 citation statements)

References 38 publications

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“…The adenovirus Bcl-x L expression vector, the GFP-nucleolin expression vector pEGF-C1 and Renilla-Bcl-x L construct were gifts of Yuichiro J. Suzuki (Georgetown University, Washington, DC), Michael Kastan (St Jude Children's Research Hospital, Memphis, TN) (Takagi et al, 2005) and George Tim Bowden (University of Arizona, Tucson, AZ) (Zhang et al, 2008), respectively. Immortalized bovine PEpCs were a gift of David McClenahan (University of Northern Iowa, Cedar Falls, IA) (McClenahan et al, 2008).…”

Section: Reagentsmentioning

confidence: 99%

Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells

Lee

Mungunsukh

Tutino

et al. 2010

Journal of Cell Science

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SummaryAngiotensin II (Ang II) is a key proapoptotic factor in fibrotic tissue diseases. However, the mechanism of Ang-II-induced cell death in endothelial cells has not been previously elucidated. Using the neutral comet assay and specific receptor antagonists and agonists, we found that Ang-II-mediated apoptosis in primary pulmonary endothelial cells required the AT2 receptor. Ang II caused cytochrome c release from the mitochondria concurrent with caspase-3 activation and DNA fragmentation, and apoptosis was suppressed by an inhibitor of Bax-protein channel formation, implicating mitochondrial-mediated apoptosis. There was no evidence that the extrinsic apoptotic pathway was involved, because caspase-9, but not caspase-8, was activated by Ang-II treatment. Apoptosis required phosphoprotein phosphatase activation, and inhibition of the SHP-2 phosphatase (encoded by Ptpn11) blocked cell death. Reduced levels of anti-apoptotic Bcl-2-family members can initiate intrinsic apoptosis, and we found that Ang-II treatment lowered cytosolic Bcl-x L protein levels. Because the protein nucleolin has been demonstrated to bind Bcl-x L mRNA and prevent its degradation, we investigated the role of nucleolin in Ang-II-induced loss of Bcl-x L . RNA-immunoprecipitation experiments revealed that Ang II reduced the binding of nucleolin to Bcl-x L mRNA in an AU-rich region implicated in instability of Bcl-x L mRNA. Inhibition of SHP-2 prevented Ang-II-induced degradation of Bcl-x L mRNA. Taken together, our findings suggest that nucleolin is a primary target of Ang-II signaling, and that Ang-II-activated SHP-2 inhibits nucleolin binding to Bcl-x L mRNA, thus affecting the equilibrium between pro-and anti-apoptotic members of the Bcl-2 family.

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Section: Reagentsmentioning

confidence: 99%

Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells

Lee

Mungunsukh

Tutino

et al. 2010

Journal of Cell Science

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“…We have previously demonstrated that lipopolysaccharide (LPS) can induce permeability changes in endothelial cells in vitro that would be consistent with vascular leakage. However, the effects are slow, requiring well over 12 h to cause measurable effects on permeability (13). It is possible that the host releases substances in the early pathological response that contribute to the extensive leakage of vascular products into the lung.…”

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confidence: 99%

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

McClenahan

Hillenbrand

Kapur

et al. 2009

Clin Vaccine Immunol

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Pneumonia in cattle is an important disease both economically and in terms of animal welfare. Recent evidence in other species has shown ATP to be an important modulator of inflammation in the lung, where it is released by activated alveolar macrophages and damaged lung cells. Whether ATP serves a similar process during infection in the bovine lung is unknown. In the present study, we examined the effects of ATP treatment on the morphology, apoptosis, and permeability of bovine pulmonary epithelial (BPE) cells and bovine pulmonary microvascular endothelial cells (BPMEC). Monolayers of BPE cells underwent striking morphological changes when exposed to ATP that included separation of the cells. Neither BPE cells nor BPMEC exhibited increased apoptosis in response to ATP. BPE cell and BPMEC monolayers displayed virtually identical increases in permeability when exposed to ATP, with a 50% change occurring within the first hour of exposure. Both cell types contained mRNA for the P2X 7 receptor, a known receptor for ATP. In BPE cells, but not BPMEC, the change in permeability in response to ATP was reversed by the addition of a P2X 7 receptor antagonist. If similar permeability changes occur in vivo, they could be a factor in vascular leakage into lung airspaces during pneumonia.Several infectious agents are involved in the bovine respiratory disease complex. Among the bacteria involved in this complex, Mannheimia haemolytica is associated with particularly severe lung inflammation that culminates in extensive lung pathology. One of the hallmark pathological changes associated with M. haemolytica pneumonia is the extensive leakage of vascular products into the lung interstitium and air spaces (24,30). We have previously demonstrated that lipopolysaccharide (LPS) can induce permeability changes in endothelial cells in vitro that would be consistent with vascular leakage. However, the effects are slow, requiring well over 12 h to cause measurable effects on permeability (13). It is possible that the host releases substances in the early pathological response that contribute to the extensive leakage of vascular products into the lung. One such possible substance is ATP.The involvement of extracellular ATP in lung inflammation is a relatively new area of research. Patients with cystic fibrosis, a chronic inflammatory lung disease in humans, have increased levels of ATP in both their sputum and lungs (4). This has been correlated with increased neutrophil numbers in the lung. In a model of asthma, extracellular ATP activated dendritic cells in the lungs, which then stimulated airway inflammation (6). Airway smooth muscle contraction, another physiologic change associated with asthma, is also stimulated by ATP (16). The effects of ATP are not always detrimental. ATP appears to have a protective effect in acute inflammation. Kolosova et al. demonstrated that a long-lasting, nonhydrolyzed form of ATP (ATP␥S) given to mice after transtracheal administration of LPS prevented increases in bronchoalveolar lavage protein and white...

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“…23,24 LPS is a potent vasodilator; it stimulates pulmonary endothelial changes consistent with the vascular leakage. 86 In addition, when administered intravenously in sheep, LPS produces clinical signs associated with the hypotension. 4 The systemic effects of LPS are considerably important in acute pasteurellosis, which causes septicemia in lambs, resulting in high mortality.…”

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confidence: 99%

Mannheimia haemolytica

2010

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Mannheimia haemolytica serotype S1 is considered the predominant cause of bovine pneumonic pasteurellosis, or shipping fever. Various virulence factors allow M haemolytica to colonize the lungs and establish infection. These virulence factors include leukotoxin (LKT), lipopolysaccharide, adhesins, capsule, outer membrane proteins, and various proteases. The effects of LKT are species specific for ruminants, which stem from its unique interaction with the bovine b2 integrin receptor present on leukocytes. At low concentration, LKT can activate bovine leukocytes to undergo respiratory burst and degranulation and stimulate cytokine release from macrophages and histamine release from mast cells. At higher concentration, LKT induces formation of transmembrane pores and subsequent oncotic cell necrosis. The interaction of LKT with leukocytes is followed by activation of these leukocytes to undergo oxidative burst and release proinflammatory cytokines such as interleukins 1, 6, and 8 and tumor necrosis factor a. Tumor necrosis factor a and other proinflammatory cytokines contribute to the accumulation of leukocytes in the lung. Formation of transmembrane pores and subsequent cytolysis of activated leukocytes possibly cause leakage of products of respiratory burst and other inflammatory mediators into the surrounding pulmonary parenchyma and so give rise to fibrinous and necrotizing lobar pneumonia. The effects of LKT are enhanced by lipopolysaccharide, which is associated with the release of proinflammatory cytokines from the leukocytes, activation of complement and coagulation cascade, and cell cytolysis. Similarly, adhesins, capsule, outer membrane proteins, and proteases assist in pulmonary colonization, evasion of immune response, and establishment of the infection. This review focuses on the roles of these virulence factors in the pathogenesis of shipping fever.

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Effects of Lipopolysaccharide andMannheimia haemolyticaLeukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells

Cited by 34 publications

References 38 publications

Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells

Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Mannheimia haemolytica

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