Proteomic Analysis Revealed the Characteristics of Key Proteins Involved in the Regulation of Inflammatory Response, Leukocyte Transendothelial Migration, Phagocytosis, and Immune Process during Early Lung Blast Injury

Abstract

Previous studies found that blast injury caused a significant increased expression of interleukin-1, IL-6, and tumor necrosis factor, a significant decrease in the expression of IL-10, an increase in Evans blue leakage, and a significant increase in inflammatory cell infiltration in the lungs. However, the molecular characteristics of lung injury at different time points after blast exposure have not yet been reported. Therefore, in this study, tandem mass spectrometry (TMT) quantitative proteomics and bioinformatics analysis were used for the first time to gain a deeper understanding of the molecular mechanism of lung blast injury at different time points. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h, and 1 w after low-intensity blast exposure. TMT quantitative proteomics and bioinformatics analysis were performed to analyze protein expression profiling in the lungs from control and blast-exposed mice, and differential protein expression was verified by Western blotting. The results demonstrated that blast exposure induced severe lung injury, leukocyte infiltration, and the production of inflammatory factors in mice. After analyzing the expression changes in global proteins and inflammation-related proteomes after blast exposure, the results showed that a total of 6861 global proteins and 608 differentially expressed proteins were identified, of which 215, 128, 187, 232, and 65 proteins were identified at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. Moreover, blast exposure-induced 177 differentially expressed proteins were associated with inflammatory responses, which were enriched in the inflammatory response regulation, leukocyte transendothelial migration, phagocytosis, and immune response. Therefore, blast exposure may induce early inflammatory response of lung tissue by regulating the expression of key proteins in the inflammatory process, suggesting that early inflammatory response may be the initiating factor of lung blast injury. These data can provide potential therapeutic candidates or approaches for the development of future treatment of lung blast injury.

Pathophysiological changes and injury markers for acute lung injury from blunt impact in infant rabbits

“…To understand the changes in inflammation during the immediate inflammatory response within 24 h, we monitored the control group and the injury groups at 0 and 24 h using serological ELISA. Serum levels of IL-6 and IL-8 increased rapidly post-injury and then decreased at 24 h ( 27 ). Some researchers found that the levels of proinflammatory factors such as IL-6, and IL-8 were significantly increased in BALF and serum of ALI/ARDS children.…”

DDAH1 Promotes Lung Endothelial Barrier Repair by Decreasing Leukocyte Transendothelial Migration and Oxidative Stress in Explosion-Induced Lung Injury

“…VCAM-1, ICAM-1, and E-selectin were reportedly upregulated in an experimental sepsis model of human umbilical vein endothelial cells [ 24 ]. ICAM-1 mRNA can also interact with Itgal, which mainly encodes a key T cell integrin, lymphocyte function-associated antigen 1(LAF1), and is considered to be an important factor in regulating T cell activation and migration [ 8 ]. Itgal also plays important roles in recruiting cells to sites of inflammation and has downstream effects on cellular signaling [ 25 ].…”

“…Inflammatory responses have been shown to be activated in explosion-induced injury [ 7 ]. In our previous study, proteomic analysis helped confirm that blast lung injury induced early inflammatory response through regulating the expression of key proteins involved in the inflammatory process [ 8 ]. Additionally, expression levels of leukocyte adhesion- (LA-) related proteins were increased by blast exposure.…”

Establishment and evaluation of an in vitro blast lung injury model using alveolar epithelial cells

“…Among all inflammatory cytokines we concentrate, IL-18 plays an important role in early inflammatory response, it is reported to promote neutrophils aggregation and lympho T cell proliferation, and mediate cytotoxic reactions (32). TNF-α is located in the upstream of the inflammatory response and mediate the synthesis of various inflammatory cytokines (14). TGF-β can inhibit cell proliferation and induce cell differentiation or apoptosis (33,34).…”

“…When the lung is exposed by blast wave, a series of physiological stress responses such as oxidative stress, inflammation, and edema often occur (10)(11)(12). Moreover, some researchers used mice to establish a blast lung injury model in vivo based on the shock tube to explore the mechanism of blast lung injury, and found that the blast wave could cause inflammation, oxidative stress and apoptosis in the lung tissues of mice (13,14). Mechanistically, damage in alveolar epithelial cells is the main cause of oxidative stress and inflammatory response, it plays an important role in blast wave-induced lung injury (15).…”