Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ischemia-reperfusion - PubMed (original) (raw)

. 2008 Jun;36(6):1846-54.

doi: 10.1097/CCM.0b013e31816f49cb.

Claus U Niemann, Kirk C Hansen, SooJinNa Choi, Xiao Su, James A Frank, Xiaohui Fang, Ryutaro Hirose, Pierre Theodore, Anil Sapru, Alma L Burlingame, Michael A Matthay

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Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ischemia-reperfusion

Jan Hirsch et al. Crit Care Med. 2008 Jun.

Abstract

Objective: Hepatic ischemia-reperfusion can be associated with acute lung injury. Alveolar epithelial type II cells (ATII) play an important role in maintaining lung homeostasis in acute lung injury.

Design: To study potentially new mechanisms of hepatic ischemia-reperfusion-induced lung injury, we examined how liver ischemia-reperfusion altered the proteome of ATII.

Setting: Laboratory investigation.

Subjects: Spontaneously breathing male Zucker rats.

Interventions: Rats were anesthetized with isoflurane. The vascular supply to the left and medial lobe of the liver was clamped for 75 mins and then reperfused. Sham-operated rats were used as controls. After 8 hrs, rats were killed.

Measurements and main results: Bronchoalveolar lavage and differential cell counts were performed, and tumor necrosis factor-alpha and cytokine-induced neutrophil chemotactic factor-1 in plasma were determined by enzyme-linked immunosorbent assay. ATII were isolated, lysed, tryptically digested, and labeled using isobaric tags (iTRAQ). The samples were fractionated by cation exchange chromatography, separated by high-performance liquid-chromatography, and identified using electrospray tandem mass spectrometry. Spectra were interrogated and quantified using ProteinProspector. Quantitative proteomics provided quantitative data for 94 and 97 proteins in the two groups. Significant changes in ATII protein content included 30% to 40% increases in adenosine triphosphate synthases, adenosine triphosphate/adenosine diphosphate translocase, and catalase (all p < .001). Following liver ischemia-reperfusion, there was also a significant increase in the percentage of neutrophils in bronchoalveolar lavage (48% +/- 26%) compared with sham-operated controls (5% +/- 3%) (p < .01), and plasma tumor necrosis factor-alpha levels were also significantly increased.

Conclusions: The proteins identified by quantitative proteomics indicated significant changes in moderators of cell metabolism and host defense in ATII. These findings provide new insights into possible mechanisms responsible for hepatic ischemia-reperfusion-related acute lung injury and suggest that ATII cells in the lung sense and respond to hepatic injury.

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Figures

Figure 1

Figure 1

A, tumor necrosis factor (TNF)-α concentration in the plasma. The TNF-α concentration in plasma of ischemia-reperfusion (I/R)-treated rats was significantly elevated at 219 ± 180 pg/mL (n = 6), whereas the cytokine had an average content of 7 ± 15 pg/mL in the plasma of normal controls (n = 5). TNF-α was not detected in plasma samples from sham operated rats. B, cytokine-induced neutrophil chemotactic factor (CINC)-1 concentration in the plasma. CINC-1 was significantly elevated in I/R-treated animals (1537 ± 279 pg/mL; n = 6) compared with both normal controls (204 ± 128 pg/mL; p < .0001) and sham-operated rats (930 ± 140 pg/mL; p < .001).

Figure 2

Figure 2

Proteins of the oxidant system. The proteins catalase, myeloperoxidase, and superoxide dismutase were significantly elevated in alveolar epithelial type II cells from rats after liver ischemia-reperfusion (I/R) but not after sham operation. The bars represent the average iTRAQ protein abundance ratio; the error bars represent the overall mean and

sd

based on the individual peptide ratios.

Figure 3

Figure 3

Enzymes of the adenosine phosphate system. The three enzymes proteins adenosine triphosphate (ATP) synthase α chain, ATP synthase β chain, and adenosine diphosphate (ADP)/ATP translocase 2 were significantly elevated in rats after both liver ischemia-reperfusion and sham operation. The bars represent the average iTRAQ protein abundance ratio; the error bars represent the overall mean and

sd

based on the individual peptide ratios.

Figure 4

Figure 4

Intracellular metabolic enzymes. There were significantly increased cellular contents in glucose regulating proteins (GRP) 75 and 78, malate dehydrogenase, L-lactate dehydrogenase (A-chain), and fatty acid synthase in rats after liver ischemia-reperfusion. In rats that had undergone sham operation, the content in these enzymes was essentially unchanged. The bars represent the average iTRAQ protein abundance ratio; the error bars represent the overall mean and

sd

based on the individual peptide ratios.

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