Inactivation of Exogenous Surfactant by Pulmonary Edema Fluid

Kobayashi, Tsutomu; Nitta, Keiko; Ganzuka, M.; Inui, Sachiko; Grossmann, Gertie; Robertson, Bengt

doi:10.1203/00006450-199104000-00005

Cited by 105 publications

(43 citation statements)

References 11 publications

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“…In addition, both pulmonary edema fluid and fibrinogen have been shown to inactivate pulmonary surfactant (25,49). Edema fluid is leaked into the lung during PCP-related inflammation, and recent studies have demonstrated that fibrinogen is synthesized in the lung during PCP (44).…”

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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Section: Fig 3 Effect Of Cd8mentioning

confidence: 99%

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

et al. 2001

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“…However, damage to the surfactant monolayer has already occurred, and a vicious circle is initiated. Protein concentration will rise in the alveolar space and result in a dose-dependent inactivation/inhibition of surfactant (18): surfactant is rate-limiting for the transfer of protein over the alveolar capillary membrane, loss of surfactant function will result in more protein influx, which, in turn, will inactivate/inhibit even more surfactant (17,18,30). Further evidence that the surfactant system is damaged and that no additional fibrosis is present comes from the maximal volume data, which are similar in both groups (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…To study the presence of histological changes in lung morphology, 1 h after instillation of the liposomes, blood was removed from the lungs by perfusion of the pulmonary arteries with warmed saline (37°C) supplemented with 20 IE heparin/ ml. Next, the lungs were fixated as previously described (17). Briefly, after perfusion, the lungs were fixed with a solution consisting of 3.6% formaldehyde and 0.25% glutaraldehyde.…”

Section: Methodsmentioning

confidence: 99%

Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function

Poelma¹,

Lachmann²,

Haitsma³

et al. 2005

Journal of Applied Physiology

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-The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca 2ϩ , Mg 2ϩ ), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved. lung; surfactant; metabolism THE ALVEOLUS IS LINED WITH a thin layer of lipids and proteins, called surfactant, and this surface active agent has an essential role in maintaining normal lung function. Pulmonary surfactant is produced by alveolar type II cells. By weight, ϳ90% of surfactant consists of lipids. Although the lipid composition varies in different species, its major component is phosphatidylcholine (70 -

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“…In addition, due to inflammatory injury of the alveolar epithelial surface leading to compromise of the air-fluid barrier, there is leakage of fluid (alveolar oedema) and serum proteins into the airspace. Both alveolar oedema [51] and serum proteins [52] can contribute to surfactant inactivation and dysfunction. Efficacy of exogenous surfactant replacement therapy in acute respiratory failure due to GBS sepsis was studied in a prospective multicentre trial [53].…”

Section: Group B Streptococcus Sepsis In Newborn Infantsmentioning

confidence: 99%

Pulmonary surfactant in newborn infants and children

Chakraborty

Kotecha

2013

Breathe

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N To understand the composition, secretory pathways and functions of pulmonary surfactant.N To review the clinical evidence regarding the use of surfactants in newborn infants and children.N To develop an understanding of rarer disorders of surfactant metabolism. N To understand recent developments and future prospects in the field of surfactants. SummaryPulmonary surfactant is a complex mixture of specific lipids, proteins and carbohydrates, which is produced in the lungs by type II alveolar epithelial cells. The mixture is surface active and acts to decrease surface tension at the air-liquid interface of the alveoli. The presence of such molecules with surface activity had been suspected since the early 1900s and was finally confirmed in the mid-1900s. Since then, the chemical, physical and biological properties of the surfactant mixture have been revealed due to the work of several groups of investigators. The surfactant mixture is an essential group of molecules to support air breathing. Thus, preterm infants, who are born with immature lungs and are surfactant deficient, develop respiratory distress syndrome after being born. Replacement of natural surfactant therapy with purified surfactant from lungs of nonhuman species is one of the most significant advances in neonatology and has resulted in improved limits of viability of preterm infants. Although preterm infants are the primary population, exogenous surfactant treatment may also have a role to play in other respiratory diseases of term-born infants and older children. HERMES syllabus link: module E.1.16

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Inactivation of Exogenous Surfactant by Pulmonary Edema Fluid

Cited by 105 publications

References 11 publications

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function

Pulmonary surfactant in newborn infants and children

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