Tumor necrosis factor-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes is partially mediated by prostaglandins.

Arias-Dı́az, Javier; Vara, Elena; Garcı́a, Cruz; Balibrea, J.L.

doi:10.1172/jci117313

Cited by 43 publications

(25 citation statements)

References 28 publications

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“…In the study by Galve-de Rochemonteix et al, alveolar macrophages were obtained from patients with pulmonary cell carcinoma. Alveolar macrophages from patients with lung cancer have shown in vitro greater TNF-␣ and IL-1 secretion than healthy controls (3,28). In the present study, these Fig.…”

Section: Discussionsupporting

confidence: 57%

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

Casals¹,

Arias-Dı́az

Valiño³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release. Am J Physiol Lung Cell Mol Physiol 284: L466-L472, 2003. First published November 15, 2002 10.1152/ajplung.00325.2002In this study we investigated the effect of acute-phase levels of C-reactive protein (CRP) on cytokine production by pulmonary macrophages in the presence or absence of pulmonary surfactant. Both human alveolar and interstitial macrophages as well as human surfactant were obtained from multiple organ donor lungs. Precultured macrophages were stimulated with LPS alone or together with IFN-␥ in the presence or absence of CRP, surfactant, and combinations. Releases of TNF-␣ and of IL-1␤ to the medium were determined. We found that CRP could modulate lung inflammation in humans by decreasing the production of proinflammatory cytokines by both alveolar and interstitial macrophages stimulated with LPS alone or together with IFN-␥. The potential interaction between CRP and surfactant phospholipids did not overcome the effect of either CRP or surfactant on TNF-␣ and IL-1␤ release by lung macrophages. On the contrary, CRP and pulmonary surfactant together had a greater inhibitory effect than either alone on the release of proinflammatory cytokines by lung macrophages.

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Section: Discussionsupporting

confidence: 57%

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

Casals¹,

Arias-Dı́az

Valiño³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In vivo, it is also possible that certain cytokines blunt the PC biosynthesis response to FC loading. For example, there is evidence that tumor necrosis factor-␣, which is synthesized and secreted by macrophages in response to a variety of factors (48,49) and is known to be present in atherosclerotic lesions (50, 51), can inhibit cellular PC biosynthesis in alveolar cells (52). We feel that the major impact of this work is that it provides Macrophages encounter and internalize atherogenic lipoproteins in the subendothelial matrix of developing lesions, thereby accumulating excess cellular cholesterol.…”

Section: Discussionmentioning

confidence: 91%

Evidence That the Initial Up-regulation of Phosphatidylcholine Biosynthesis in Free Cholesterol-loaded Macrophages Is an Adaptive Response That Prevents Cholesterol-induced Cellular Necrosis

Tabas

Marathe

Keesler

et al. 1996

Journal of Biological Chemistry

102

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Macrophages in atherosclerotic lesions accumulate free cholesterol (FC) as well as cholesteryl ester and appear to have high rates of phospholipid (PL) synthesis and increased PL mass. Previous short term (i.e. 24 h) studies with cultured macrophages have shown that these cells respond to FC loading by up-regulating phosphatidylcholine biosynthesis. We propose that this response is adaptive by keeping the FC:PL ratio in the macrophages from reaching toxic levels. We further propose that one cause of macrophage necrosis, a prominent and important event in atherosclerosis, is an eventual decrease of this adaptive response. To explore these ideas, cultured macrophages were loaded with FC for up to 4 days and assayed for phosphatidylcholine biosynthesis, FC and PL mass, and cytotoxicity. For the first 24 h, cellular phosphatidylcholine biosynthesis and FC and PL mass increased 3-4-fold, and thus the FC:PL molar ratio was prevented from reaching very high levels; at this point, there were no overt signs of cytotoxicity. Over the next 24 -48 h, however, phosphatidylcholine biosynthesis, and then phosphatidylcholine mass, began to decrease. Initially, the macrophages remained healthy and continued to accumulate FC, but eventually these macrophages, but not unloaded macrophages, became necrotic (swollen organelles and disrupted membranes). Lipoprotein dose studies indicated a close relationship between the onset of macrophage necrosis and the FC:PL ratio. To test further the causal nature of these relationships, cellular FC and PL mass were independently manipulated by using high density lipoprotein 3 (HDL 3 ) to decrease cellular FC and choline depletion to decrease cellular PC. As predicted by our hypotheses, HDL 3 protected FC-loaded macrophages from necrosis, whereas choline depletion accelerated cytotoxic changes. These findings support the idea that the initial increase in phosphatidylcholine biosynthesis in FC-loaded macrophages is an adaptive response that prevents cholesterol-induced macrophage necrosis. We propose that an eventual failure of the PL response in foam cells may represent one cause of macrophage necrosis in advanced atherosclerotic lesions.

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“…Activated macrophages release numerous proteases that may lead to surfactant inactivation (37). In addition, macrophages release tumor necrosis factor alpha (TNF-␣), which has negative effects on surfactant synthesis (2,34,56) and may also play a role in the recruitment and activation of neutrophils (54). Large numbers of neutrophils were found in BAL fluid from both reconstituted, P. carinii-infected mice and P. cariniiinfected CD4…”

Section: Fig 3 Effect Of Cd8mentioning

confidence: 99%

“…A host of mediators and substances capable of affecting pulmonary surfactant and its activity are present in the lung during PCP. TNF-␣, for example, inhibits gene expression of SP-A and -B (34,56), as well as the synthesis of surfactant phospholipids in alveolar epithelial cells (2). TNF-␣ also increases protease release from macrophages and neutrophils and can contribute to pulmonary edema by increasing the permeability of the alveous-capillary barrier (35,37,45).…”

Section: Fig 3 Effect Of Cd8mentioning

confidence: 99%

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

et al. 2001

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During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonary inflammation correlates directly with the severity of lung function deficits. Therefore, studies were undertaken to determine whether the host inflammatory response contributes to PCP-related respiratory impairment, at least in part, by disrupting the pulmonary surfactant system. Protein and phospholipid content and surfactant activity were measured in the lavage fluid of infected mice in either the absence or presence of an inflammatory response. At 9 weeks postinfection with P. carinii, nonreconstituted SCID mice exhibited no signs of pulmonary inflammation, respiratory impairment, or surfactant dysfunction. Lavage fluid obtained from these mice had protein/phospholipid (Pr/PL) ratios (64% ؎ 4.7%) and minimum surface tension values (4.0 ؎ 0.9 mN/m) similar to those of P. carinii-free control mice. However, when infected SCID mice were immunologically reconstituted, an intense inflammatory response ensued. Pr/PL ratios (218% ؎ 42%) and minimum surface tension values (27.2 ؎ 2.7 mN/m) of the lavage fluid were significantly elevated compared to those of the lavage fluid from infected, nonreconstituted mice (P < 0.05). To examine the specific role of CD8 ؉ T-cell-mediated inflammation in surfactant dysfunction during PCP, mice with defined T-cell populations were studied. P. carinii-infected, CD4 ؉ -depleted mice had elevated lavage fluid Pr/PL ratios (126% ؎ 20%) and elevated minimum surface tension values (16.3 ؎ 1.0 mN/m) compared to normal mice (P < 0.05). However, when infected mice were additionally depleted of CD8 ؉ cells, Pr/PL ratios were normal and surfactant activity was improved. These findings demonstrate that the surfactant pathology associated with PCP is related to the inflammatory process rather than being a direct effect of P. carinii. Moreover, CD8؉ lymphocytes are involved in the mechanism leading to surfactant dysfunction.Pneumocystis carinii pneumonia (PCP) is a life-threatening opportunistic infection of the immunocompromised host. The clinical hallmark of PCP at presentation is tachypnea and hypoxia. Few rales are present upon auscultation of the chest, and X ray shows a diffuse pattern of alveolar disease. The mechanism by which P. carinii produces this clinical picture is poorly understood. One possible contributor to the constellation of signs and symptoms of PCP is direct or indirect disruption of the pulmonary surfactant system. Surfactant is a macromolecular complex of various phospholipids and specific proteins that regulates surface tension at the air-liquid interface within the alveolus. Surfactant-mediated reduction and variation of surface tension stabilize alveolar inflation and deflation behavior and reduce the work of breathing. Loss of surfactant activity results in decreased lung compliance, atelectasis, and impaired gas exchange.There have been several experimental observations that suggest that P. carinii has the potential to cause physiological disruption of the surfactant system. Sheehan et al. ...

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Tumor necrosis factor-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes is partially mediated by prostaglandins.

Cited by 43 publications

References 28 publications

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

Evidence That the Initial Up-regulation of Phosphatidylcholine Biosynthesis in Free Cholesterol-loaded Macrophages Is an Adaptive Response That Prevents Cholesterol-induced Cellular Necrosis

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

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