Protein, cell, and LTB4 concentrations of lung edema fluid produced by high capillary pressures in rabbit

Tsukimoto, K.; Yoshimura, Nobuyuki; Ichioka, Masahiko; Tojo, Naoko; Miyazato, Itsuro; Marumo, Fumiaki; Mathieu-Costello, Odile; West, J. B.

doi:10.1152/jappl.1994.76.1.321

Cited by 44 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the levels were lower than those in patients with ALI/ ARDS, the detection of RAGE in the edema fluid and the moderate elevation of RAGE in the plasma of patients with severe hydrostatic pulmonary edema suggests that there may be some low-level injury to the alveolar epithelium in these patients that may be related to the stress-induced epithelial changes reported by West and colleagues (31,32) or to the effects of positive pressure ventilation in patients with severe lung edema. Our prior studies of pulmonary edema fluid from hydrostatic patients demonstrate some low level of inflammation and detectable protease activity in most patients, although the magnitude of inflammation is less than in patients with ALI (28,(33)(34)(35).…”

Section: Rage As a Marker Of Alveolar Type I Epithelial Cell Injury Imentioning

confidence: 71%

Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

Uchida

Shirasawa

Ware

et al. 2006

Am J Respir Crit Care Med

412

397

View full text Add to dashboard Cite

Rationale: Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung. Objectives: To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury. Methods: Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI; n ϭ 22) and hydrostatic pulmonary edema (n ϭ 11). Main Results: In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized ‫ف‬ 48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p Ͻ 0.0001). The median edema fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p Ͻ 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p Ͻ 0.001) or patients with hydrostatic pulmonary edema (p Ͻ 0.05). Conclusion: RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.Keywords: acute respiratory distress syndrome; alveolar epithelium; biological markers; pulmonary edemaReceptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung (1, 2). Although it is also expressed in endothelial cells in large vessels (3, 4) and nervous tissues (5, 6), the transcript of RAGE is most prominent in the lung (3) and apparently not expressed in lung microvascular endothelia (7,8). Immunoelectron microscopy of RAGE demonstrated that its expression is localized to the basal membrane of alveolar type I epithelial cells (7,8 binding site and two C-type immunogloblin-like regions), a transmembrane domain, and a cytosolic tail, that are essential for post-RAGE signaling (9). In general, RAGE is a multiligandbinding receptor that can bind advanced glycation end products, amyloid ␤-peptide, S100 proteins, and high-mobility group box-1 (10-12). RAGE-ligand interaction results in intracellular signaling, which leads to activation of the proinflammatory transcription factor nuclear factor-B (NF-B). This cellular activation is related to inflammatory processes or tissue injury, such as diabetic microvascular injury, amyloidosis, and immune-inflammatory process (10-12). RAGE knockout mice were recently reported to be resistant to septic shock induced by cecal ligation and puncture (13), suggesting that RAGE potentially plays a role in systemic acute inflammation. However, the biochemical characteristics of RAGE in the lung in response to acute lung injury (ALI) have not been determined.Alveolar type I epithe...

show abstract

Section: Rage As a Marker Of Alveolar Type I Epithelial Cell Injury Imentioning

confidence: 71%

Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

Uchida

Shirasawa

Ware

et al. 2006

Am J Respir Crit Care Med

412

397

View full text Add to dashboard Cite

show abstract

“…In addition, the association of noninfective LRT symptoms with high Q 'p/Q 's, and noninfective LRT symptoms with low concentrations of ELF total protein are compatible with a clinically significant increase in alveolar fluid. In animal studies, increased pulmonary capillary transmural pressure (Ptm) from left atrial occlusion, results in the formation of proteinrich "permeability" oedema in the alveoli [29]. However, these experiments utilize acute and massive elevations in Ptm and are not comparable with the chronic, flowrelated changes in Ptm in human CHD.…”

Section: Age Monthsmentioning

confidence: 99%

Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease

Grigg¹,

Kleinert²,

Woods³

et al. 1996

European Respiratory Journal

View full text Add to dashboard Cite

This study applied bronchoalveolar lavage (BAL) to children with congenital heart disease (CHD) prior to elective cardiac catheterization (n=48), to determine the influence of pulmonary blood flow and viral infection on the alveolar epithelial lining fluid (ELF) concentration of leucocytes, protein and endothelin-1 (ET-1).Lower respiratory tract (LRT) viral infection was defined as either a positive immunofluorescence for virus, or a virus cultured from the bronchoalveolar lavage fluid (BALF). Haemodynamic status was determined at cardiac catheterization. Normative data for BALF, but not ELF parameters, were obtained from 26 asymptomatic, noninfected normal children undergoing elective surgery.In the absence of LRT infection, the BALF macrophage, lymphocyte and neutrophil differential in CHD was not significantly different from the normal controls. In CHD, both increased pulmonary-to-systemic flow ratio (Q'p/Q's) and increased pulmonary artery-to-left ventricular pressure ratio PAP/LVP were associated with a decrease in ELF protein (r s = -0.59; p<0.0001; and r s = -0.50; p<0.0001 respectively). A respiratory virus was isolated from the BALF in 8 (17%) of CHD children. Virus isolation was associated with an increased ELF total protein (p<0.05 vs no infection), a decreased alveolar macrophage differential count (p<0.01), and an increased neutrophil differential count (p<0.05). ET-1 was detected in the BALF of 83% of the noninfected CHD children compared to only 23% of the controls (p<0.001). ELF ET-1 concentrations did not correlate with haemodynamic status in CHD, but were up to 100 times higher than paired plasma levels.We conclude that, in congenital heart disease, both lower respiratory tract viral infection and increased pulmonary blood flow and/or pulmonary vascular pressure influence the alveolar milieu. High alveolar epithelial lining fluid concentrations of endothelin-1 occur in congenital heart disease, but the stimulus for pulmonary endothelin-1 production is unclear.

show abstract

“…Accompanying this is increased permeability of the lung to protein and red blood cells, as measured by increased concentrations in bronchoalveolar lavage fluid [6]. Leukotriene (LT)B 4 concentration is also increased in bronchoalveolar lavage fluid [6], perhaps representing cellular activation by exposed basement membrane. Similar findings are observed in some humans following maximal exercise in normoxia [7] where bronchoalveolar lavage fluid contains increased concentrations of red cells, protein and LTB 4 thought to result from high pulmonary capillary pressures.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Similar findings are observed in some humans following maximal exercise in normoxia [7] where bronchoalveolar lavage fluid contains increased concentrations of red cells, protein and LTB 4 thought to result from high pulmonary capillary pressures. In both of these instances, the blood-gas barrier retains sieving function for large molecular weight proteins [6]. However, in established HAPE, permeability to macromolecules is increased [8], and an inflammatory response of the lung to hypoxia has been suggested as an alternate mechanism [9].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Stress failure and high-altitude pulmonary oedema: mechanistic insights from physiology

Hopkins¹

2010

Eur Respir J

View full text Add to dashboard Cite

H igh-altitude pulmonary oedema (HAPE) is a potentially fatal altitude illness affecting individuals within 2-4 days of rapid ascent to altitudes above 3,000 m. Although a minority of high-altitude travellers develop HAPE [1], there is some suggestion that many develop subclinical fluid accumulation without overt alveolar flooding [2]. The inciting mechanism of the injury to the lung in HAPE still generates some controversy. However, there is an evergrowing body of evidence that mechanical injury to the pulmonary capillaries induced by high transmural pressures starts a cascade of events that ultimately results in the development of HAPE. This injury, termed ''stress failure'' described by WEST et al. [3], refers to mechanically induced breaks in the blood-gas barrier, and these have been suggested to be important the pathophysiology of a number of human diseases [4].In animals, when pulmonary capillaries are subjected to increased transmural pressure, ultrastructural changes consisting of discrete areas of damage to the blood-gas barrier, with rupture of the capillary endothelium, extracellular matrix and the alveolar epithelium, interspersed with large areas of structurally intact blood-gas barrier are observed [5]. Accompanying this is increased permeability of the lung to protein and red blood cells, as measured by increased concentrations in bronchoalveolar lavage fluid [6]. Leukotriene (LT)B 4 concentration is also increased in bronchoalveolar lavage fluid [6], perhaps representing cellular activation by exposed basement membrane. Similar findings are observed in some humans following maximal exercise in normoxia [7] where bronchoalveolar lavage fluid contains increased concentrations of red cells, protein and LTB 4 thought to result from high pulmonary capillary pressures. In both of these instances, the blood-gas barrier retains sieving function for large molecular weight proteins [6]. However, in established HAPE, permeability to macromolecules is increased [8], and an inflammatory response of the lung to hypoxia has been suggested as an alternate mechanism [9]. In addition, some authors have suggested that HAPE results from altered sodium and water handling by the susceptible lung [10].Stress failure has been suggested to be important in the development of HAPE largely because of the relationship between high pulmonary vascular pressures and the development of HAPE. A previous history of HAPE is the single greatest predictor of the development of HAPE in future exposures and HAPE-susceptible individuals generally have augmented hypoxic pulmonary vasoconstriction and increased pulmonary vascular pressures when exposed to hypoxia [11][12][13][14][15] and exercise [16]. In addition, drugs such as sidenafil, nifedipine, tadaphil and dexamethasone reduce pulmonary vascular pressures and reduce the severity of HAPE [17,18] or prevent the development when administered prophylactically [19]. Since the primary site of hypoxic pulmonary vasoconstriction is thought to be pre-capillary, hypoxic pulmonary vasoconst...

show abstract

Protein, cell, and LTB4 concentrations of lung edema fluid produced by high capillary pressures in rabbit

Cited by 44 publications

References 0 publications

Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease

Stress failure and high-altitude pulmonary oedema: mechanistic insights from physiology

Contact Info

Product

Resources

About