Predictors of Early Acute Lung Injury at a Combat Support Hospital: A Prospective Observational Study

Edens, Jason W.; Chung, Kevin K.; Pamplin, Jeremy; Allan, Patrick F.; Jones, John A.; King, Booker T.; Cancio, Leopoldo C.; Renz, Evan M.; Wolf, Steven E.; Wade, Charles E.; Holcomb, John B.; Blackbourne, Lorne H.

doi:10.1097/ta.0b013e3181e44a32

Cited by 39 publications

(33 citation statements)

References 28 publications

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“…The hyperactivation of calpain-2 and the increased expression of PTP1B were noted in a number of human cancers (52), as well as in Type 2 diabetes (3,53). Interestingly, individuals with Type 2 diabetes appear to be protected against sepsis-induced ALI (54)(55)(56). We speculate that a component of this observed protection is perhaps mediated by the overexpression of PTP1B and increased cleavage by calpain-2, resulting in an abundance of cytosolic PTP1B that is free from Nox-4-mediated oxidation and inhibition.…”

Section: Discussionmentioning

confidence: 99%

Protection against LPS-Induced Pulmonary Edema through the Attenuation of Protein Tyrosine Phosphatase–1B Oxidation

Grinnell

Chichger

Braza

et al. 2012

Am J Respir Cell Mol Biol

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One hallmark of acute lung injury is the disruption of the pulmonary endothelial barrier. Such disruption correlates with increased endothelial permeability, partly through the disruption of cell-cell contacts. Protein tyrosine phosphatases (PTPs) are known to affect the stability of both cell-extracellular matrix adhesions and intercellular adherens junctions (AJs). However, evidence for the role of select PTPs in regulating endothelial permeability is limited. Our investigations noted that the inhibition of PTP1B in cultured pulmonary endothelial cells (ECs), as well as in the vasculature of intact murine lungs via the transient overexpression of a catalytically inactive PTP1B, decreased the baseline resistance of cultured EC monolayers and increased the formation of edema in murine lungs, respectively. In addition, we observed that the overexpression of wild-type PTP1B enhanced basal barrier function in vitro. Immunohistochemical analyses of pulmonary ECs and the coimmunoprecipitation of murine lung homogenates demonstrated the association of PTP1B with the AJ proteins b-catenin, p120-catenin, and VE-cadherin both in vitro and ex vivo. Using LPS in a model of sepsis-induced acute lung injury, we showed that reactive oxygen species were generated in response to LPS, which correlated with enhanced PTP1B oxidation, inhibited phosphatase activity, and attenuation of the interactions between PTP1B and b-catenin, as well as enhanced b-catenin tyrosine phosphorylation. Finally, the overexpression of a cytosolic PTP1B fragment, shown to be resistant to nicotinamide adenine dinucleotide phosphate-reduced oxidase-4 (Nox4)-mediated oxidation, significantly attenuated LPS-induced endothelial barrier dysfunction and the formation of lung edema, and preserved the associations of PTP1B with AJ protein components, independent of PTP1B phosphatase activity. We conclude that PTP1B plays an important role in maintaining the pulmonary endothelial barrier, and PTP1B oxidation appears to contribute to sepsis-induced pulmonary vascular dysfunction, possibly through the disruption of AJs.

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Section: Discussionmentioning

confidence: 99%

Protection against LPS-Induced Pulmonary Edema through the Attenuation of Protein Tyrosine Phosphatase–1B Oxidation

Grinnell

Chichger

Braza

et al. 2012

Am J Respir Cell Mol Biol

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“…Neutrophils infiltrate the inflamed site and generate superoxide anion (O 2 •− ) and associated reactive oxygen species (ROS) 2 , as well as secreting a myriad of proteolytic enzymes that can damage surrounding cells and cause an inflammatory response [3]. Many acute and chronic inflammatory lung diseases, including acute lung injury (ALI) [4], acute respiratory distress syndrome (ARDS) [5], and chronic obstructive pulmonary disease (COPD) [6], are characterized by neutrophil-dominated inflammation. Therefore, suppression of neutrophil activation by drugs seems to be a useful way to treat inflammatory lung diseases.…”

mentioning

confidence: 99%

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4

Tsai

Chung

et al. 2015

Free Radical Biology and Medicine

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“…In the combat setting, PC is likely to result from the passage of projectiles through the parenchyma of the lungs [12,17,18]. The biological plausibility for the present study is that PC results in localized endothelial damage which is a potential source of coagulation disturbances following acute injury.…”

Section: Introductionmentioning

confidence: 78%

Untitled

2015

ETS

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Introduction: Trauma patients presenting with coagulopathy are four times more likely to die. After observing patients presenting with isolated severe Pulmonary Contusion (PC) on admission Chest X-ray (CXR) who were also coagulopathic, we hypothesized that patients with PC on admission CXR were more likely to be coagulopathic than other trauma patients. Methods:This was an IRB approved, single-center, retrospective cohort study of patients admitted over an 18 month period. Data were obtained from the trauma registry and medical records including demographics, laboratory values, injury severity scores, coagulation parameters and PC diagnostic modality. Patients on anticoagulants were excluded. The PC group consisted of patients diagnosed with PC by admission CXR. The control group were those patients without a PC or those diagnosed only by CT. Coagulopathy was defined as INR>1.4 or PTT>35 seconds. The PC group was further stratified into mild, moderate or severe PC. Data were analyzed with univariate analyses followed by development of a logistic regression model. Significance was set at p<0.05. Results:The PC group contained 189 subjects and controls 333. As expected ISS was higher in the PC group (25 vs 21) as was AIS chest (3 vs 1); both p<0.001. The prevalence of coagulopathy was also greater in PC (31% vs. 17%, p<0.001). After adjusting for ISS, PC patients were more likely to be coagulopathic (OR=1.76, 95% CI: 1.12-2.75) and had higher 24 hour (7% vs 3%, p=0.04) and overall mortality rates (15% vs 7%, p=0.006). The prevalence of coagulopathy increased with severity of pulmonary contusion in PC patients (Mild

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Predictors of Early Acute Lung Injury at a Combat Support Hospital: A Prospective Observational Study

Cited by 39 publications

References 28 publications

Protection against LPS-Induced Pulmonary Edema through the Attenuation of Protein Tyrosine Phosphatase–1B Oxidation

Protection against LPS-Induced Pulmonary Edema through the Attenuation of Protein Tyrosine Phosphatase–1B Oxidation

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4

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