A Novel Alveolar Type I Cell–Specific Biochemical Marker of Human Acute Lung Injury

Newman, Valerie; Gonzalez, Robert; Matthay, Michael A.; Dobbs, Leland G.

doi:10.1164/ajrccm.161.3.9901042

Cited by 42 publications

(26 citation statements)

References 32 publications

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“…However, HTI 56 , a human ATI-cell-specific protein, has been measured in oedema fluid and plasma from patients with established ARDS. The concentration of HTI 56 was significantly elevated in both oedema fluid and plasma from patients with ARDS in comparison to those from hydrostatic pulmonary oedema patients [100]. These data suggest that ATI-cell-specific membrane proteins may be sensitive markers of alveolar epithelial injury in patients with, and at-risk of, ALI or ARDS.…”

Section: Expression Of Alveolar Epithelial Type I Cell-selective Protmentioning

confidence: 72%

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

McElroy

Kasper²

2004

European Respiratory Journal

116

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Ultrastructural studies demonstrate that alveolar epithelial type I cell damage is frequently observed in acute and chronic lung diseases.This article discusses the use of cell-selective proteins as markers for the investigation of injury and repair of the alveolar epithelium. The utility of proteins specific to alveolar epithelial type I cells as diagnostic markers of alveolar epithelial injury in acute lung injury is considered, and expression of proteins selective for alveolar epithelial type I cells in lungs following injury and in fibrosis are discussed. Eur Respir J 2004; 24: 664-673.

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Section: Expression Of Alveolar Epithelial Type I Cell-selective Protmentioning

confidence: 72%

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

McElroy

Kasper²

2004

European Respiratory Journal

116

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“…Researchers have sought a specific marker of lung injury in the alveolar lining fluid that may aid in the diagnosis or prognosis of the disease (10,25,26). Conner et al (10) have reported that patients with acute respiratory distress syndrome have increased levels of sICAM-1 in lung edema fluid compared with serum.…”

Section: Discussionmentioning

confidence: 99%

Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury

Mendez¹,

Morris²,

Wilcoxen³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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is an adhesion molecule constitutively expressed in abundance on the cell surface of type I alveolar epithelial cells (AEC) in the normal lung and is a critical participant in pulmonary innate immunity. At many sites, ICAM-1 is shed from the cell surface as a soluble molecule (sICAM-1). Limited information is available regarding the presence, source, or significance of sICAM-1 in the alveolar lining fluid of normal or injured lungs. We found sICAM-1 in the bronchoalveolar lavage (BAL) fluid of normal mice (386 Ϯ 50 ng/ml). Additionally, sICAM-1 was spontaneously released by murine AEC in primary culture as type II cells spread and assumed characteristics of type I cells. Shedding of sICAM-1 increased significantly at later points in culture (5-7 days) compared with earlier time points (3-5 days). In contrast, treatment of AEC with inflammatory cytokines had limited effect on sICAM-1 shedding. BAL sICAM-1 was evaluated in in vivo models of acute lung injury. In hyperoxic lung injury, a reversible process with a major component of leak across the alveolar wall, BAL fluid sICAM-1 only increased in parallel with increased alveolar protein. However, in lung injury due to FITC, there were increased levels of sICAM-1 in BAL that were independent of changes in BAL total protein concentration. We speculate that after lung injury, changes in sICAM-1 in BAL fluid are associated with progressive injury and may be a reflection of type I cell differentiation during reepithelialization of the injured lung. alveolar epithelial cell; differentiation; aquaporin-5; cell culture; CD54INTERCELLULAR ADHESION MOLECULE-1 (ICAM-1) is an ϳ100-kDa protein belonging to the immunoglobulin superfamily that is involved in leukocyte trafficking and lymphocyte activation (37). ICAM-1 is a transmembrane protein that is the counterreceptor for the ␤ 2 -integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), found on leukocytes. ICAM-1 expression can be induced on most structural cells, including endothelial cells, fibroblasts, and epithelial cells, by inflammatory cytokines (37). In contrast, in the normal lung, ICAM-1 is constitutively expressed in abundance on the apical surface of type I alveolar epithelial cells (AEC), but not on type II AEC in the absence of inflammatory stimulation (9,19,32). Similar to markers such as aquaporin-5 (AQP5) and RTI40 (6, 27, 41), constitutive ICAM-1 expression is a feature of type I, but not type II, AEC in the normal lung. Furthermore, when type II cells are isolated from rats, ICAM-1 expression is induced under culture conditions favoring expression of type I AEC characteristics (9). Previously, we have shown that absence or neutralization of ICAM-1 on AEC in vivo impairs function, but not recruitment, of leukocytes in the setting of pneumonia due to Klebsiella pneumoniae (19). Moreover, blockade of ICAM-1 in vitro results in decreased macrophage mobility (20), phagocytosis, and killing of K. pneumoniae (19).In addition to its expression on the cell surface of endothelial cells, ICAM-1 is shed from that surface...

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“…Newman and colleagues (15,42) reported that HTI56 is another alveolar type I cell specific protein that can be used as a marker in human ALI. However, in that study, the quantification of HTI56 was based on the standard curve generated by only partially purified HTI56, which was purified from normal lung tissue obtained from a resected lung specimen (15). In addition, HTI56 is poorly soluble in aqueous media and therefore difficult to assay.…”

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

confidence: 99%

“…In this context, some alveolar type I epithelial cell proteins have been demonstrated to be markers of the severity of lung injury in animal and human studies (14,15). Because of the new evidence regarding high concentrations of RAGE in the lung apparently localized primarily to alveolar epithelial type I cells (1,2), we hypothesized that RAGE may be a useful biochemical marker of alveolar type I epithelial cell injury in ALI and ARDS.…”

mentioning

confidence: 99%

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

404

397

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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...

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A Novel Alveolar Type I Cell–Specific Biochemical Marker of Human Acute Lung Injury

Cited by 42 publications

References 32 publications

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury

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

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