Cytochrome b5 and Cytokeratin 17 Are Biomarkers in Bronchoalveolar Fluid Signifying Onset of Acute Lung Injury

Abstract

Acute lung injury (ALI) is characterized by pulmonary edema and acute inflammation leading to pulmonary dysfunction and potentially death. Early medical intervention may ameliorate the severity of ALI, but unfortunately, there are no reliable biomarkers for early diagnosis. We screened for biomarkers in a mouse model of ALI. In this model, inhalation of S. aureus enterotoxin A causes increased capillary permeability, cell damage, and increase protein and cytokine concentration in the lungs. We set out to find predictive biomarkers of ALI in bronchoalveolar lavage (BAL) fluid before the onset of clinical manifestations. A cutting edge proteomic approach was used to compare BAL fluid harvested 16 h post S. aureus enterotoxin A inhalation versus BAL fluid from vehicle alone treated mice. The proteomic PF 2D platform permitted comparative analysis of proteomic maps and mass spectrometry identified cytochrome b5 and cytokeratin 17 in BAL fluid of mice challenged with S. aureus enterotoxin A. Validation of cytochrome b5 showed tropic expression in epithelial cells of the bronchioles. Importantly, S. aureus enterotoxin A inhalation significantly decreased cytochrome b5 during the onset of lung injury. Validation of cytokeratin 17 showed ubiquitous expression in lung tissue and increased presence in BAL fluid after S. aureus enterotoxin A inhalation. Therefore, these new biomarkers may be predictive of ALI onset in patients and could provide insight regarding the basis of lung injury and inflammation.

Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

“…Treatment of WT mice with ozone resulted in a marked upregulation of cytochrome b5 expression, an indicator of acute lung injury and oxidative stress (Rodriguez-Ariza et al , 2005; Menoret et al , 2012) (Fig. 8).…”

“…Cytochrome b5 is a highly conserved protein that participates in the oxidation of endogenous and xenobiotic substances (Vergeres and Waskell, 1995; Schenkman and Jansson, 2003; Menoret et al , 2012). It is rapidly upregulated in the lung after enterotoxin inhalation and is thought to be an early marker of acute lung injury, inflammation and oxidative stress (Menoret et al , 2012).…”

“…It is rapidly upregulated in the lung after enterotoxin inhalation and is thought to be an early marker of acute lung injury, inflammation and oxidative stress (Menoret et al , 2012). Consistent with ozone-induced oxidative stress and lung injury, we found that cytochrome b5 expression was upregulated in the lung after ozone.…”

TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation

“…Furthermore, SEA inhalation also recapitulates a common complication in sepsis, acute lung injury. The lungs of exposed mice show elevated proteins, presence of red blood cells and increased levels of cytokines (23, 24). Using the SEA model of SIRS, we sought to study systemic immune responses occurring immediately after SEA administration.…”

Comparative Proteomic Analysis of Rat Bronchoalveolar Lavage Fluid after Exposure to Zinc Oxide Nanoparticles

“…12) Proteomic techniques are increasingly being applied to investigate associations between di erentially expressed proteins in BALF and various lung disorders such as idiopathic pulmonary brosis (IPF), 13,14) invasive pulmonary aspergillosis, 15) and acute lung injury. 9,16,17) In addition, BALF has also been used to investigate the mechanisms of lung injury associated with exposure to ambient air containing oil mist, 18) metal fumes, 19) carbon black, 20) silver NPs, 21) and ZnO NPs. 3,22) A previous study showed that the oxidative stress marker, 8-hydroxydeoxyguanosine, was signi cantly increase in BALF of Sprague-Dawley (SD) rats that had been exposed to high dose of 35-nm ZnO particles.…”