Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase

Abstract

BackgroundDespite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking.MethodsRecent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery.Results135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase.ConclusionsGiven the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.

Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury

“…Data from the model presented here echo this published clinical data, suggesting that anti-inflammatory cytokine production occurs rapidly in the lung following injury. Clinical studies have also reported that macrophage numbers in the airway do not change between the acute phase of ARDS and resolution; however, neutrophil numbers are subject to change based on disease state (12). We observed a similar phenotype in our model of acute exposure to plywood smoke.…”

“…lowing injury (12,22,29). Experiments using hickory wood chips (untreated/seasoned) resulted in similar changes in protein concentration and cell numbers.…”

Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide‐induced apoptosis partially by inhibiting the Wnt/β‐catenin pathway

“…Sepsis is the leading cause of ALI/ARDS. AM is responsible for the efficient clearance of apoptotic neutrophils by phagocytosis, through which AMs secrete antiinflammatory cytokines, such as TGF-b and interleukin (IL)-10, to prevent further tissue injury and perpetuated inflammation (von Knethen and Brune, 2000;Feng et al, 2011;Dong et al, 2013). AM is responsible for the efficient clearance of apoptotic neutrophils by phagocytosis, through which AMs secrete antiinflammatory cytokines, such as TGF-b and interleukin (IL)-10, to prevent further tissue injury and perpetuated inflammation (von Knethen and Brune, 2000;Feng et al, 2011;Dong et al, 2013).…”

“…Sepsis is the leading cause of ALI/ARDS. Given that resident alveolar macrophages (AMs) serve as the primary phagocytes responsible for removing infectious, toxic or allergenic particles from the airways (Shibata et al, 2001), its role in the pathogenesis of ALI/ARDS has recently been highly appreciated (Dong et al, 2013). AM is responsible for the efficient clearance of apoptotic neutrophils by phagocytosis, through which AMs secrete antiinflammatory cytokines, such as TGF-b and interleukin (IL)-10, to prevent further tissue injury and perpetuated inflammation (von Knethen and Brune, 2000;Feng et al, 2011;Dong et al, 2013).…”

“…Given that resident alveolar macrophages (AMs) serve as the primary phagocytes responsible for removing infectious, toxic or allergenic particles from the airways (Shibata et al, 2001), its role in the pathogenesis of ALI/ARDS has recently been highly appreciated (Dong et al, 2013). AM is responsible for the efficient clearance of apoptotic neutrophils by phagocytosis, through which AMs secrete antiinflammatory cytokines, such as TGF-b and interleukin (IL)-10, to prevent further tissue injury and perpetuated inflammation (von Knethen and Brune, 2000;Feng et al, 2011;Dong et al, 2013). However, evidence in vivo and in vitro indicates that cell apoptosis is a common mechanism in the pathogenesis of ALI/ARDS, including AMs, polymorphonuclear leukocytes (PMNs), epithelial, and endothelial cells (Matute-Bello et al, 1997;Kitamura et al, 2001;Lu et al, 2002).…”