A study of the biologic activity of trauma-hemorrhagic shock mesenteric lymph over time and the relative role of cytokines

Davidson, Marson T.; Deitch, Edwin A.; Lu, Quan; Osband, Adena J.; Feketeova, Eleonora; Németh, Zoltán; Haskó, György; Xu, Da-Zhong

doi:10.1016/j.surg.2003.12.012

Cited by 73 publications

(43 citation statements)

References 19 publications

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“…Collectively, basic bench work with rodent models of hemorrhagic shock from Deitch, et al and our lab have shown PSML to contain factors that can incite acute lung injury through mechanisms of endothelial inflammation and apoptosis as well as neutrophil priming (3)(4)(5)(16)(17)(18)(19)(20). Current research in this area has emphasized identifying the toxic bioactive mediators in PSML.…”

Section: Discussionmentioning

confidence: 93%

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Jordan

Moore

Damle

et al. 2007

Journal of Surgical Research

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Background-Gelsolin is a plasma protein that functions to depolymerize actin filaments preventing capillary plug formation following tissue injury. It also functions to mediate the inflammatory response by binding proinflammatory lipids such as lysophosphatidic acid, sphingosine-1-phosphate and phosphoinositides. Clinically, reduced gelsolin concentrations have been associated with increased mortality in critically ill, trauma and burn patients. We have previously shown that following hemorrhagic shock with splanchnic hypoperfusion, mesenteric lymph contains lipid components that cause neutrophil and EC activation and that protein concentrations are severely diluted due to resuscitation. We hypothesized that lipid binding proteins such as gelsolin may be depleted after trauma/hemorrhagic shock leading to increased lipid bioactivity.

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Section: Discussionmentioning

confidence: 93%

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Jordan

Moore

Damle

et al. 2007

Journal of Surgical Research

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“…The mechanisms of gut reperfusion-induced lung injury, while not completely elucidated, center on 1) infiltration and/or activation of lung neutrophils by circulating soluble factors (i.e., cytokines) induced by damaged cells/tissues (9, 16) and 2) infiltration and/or activation of lung neutrophils by factors derived from the mesenteric lymph (7,25,38). However, the effects of kidney IRI on subsequent lung dysfunction have not been studied extensively, and clearly, the potential molecular mechanisms involved remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy

Hassoun

Grigoryev²,

Lie

et al. 2007

American Journal of Physiology-Renal Physiology

189

168

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Hassoun HT, Grigoryev DN, Lie ML, Liu M, Cheadle C, Tuder RM, Rabb H. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol 293: F30-F40, 2007. First published February 27, 2007 doi:10.1152/ajprenal.00023.2007.-Acute kidney injury (AKI) is associated with significant mortality, which increases further when combined with acute lung injury. Experiments in rodents have shown that kidney ischemia-reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 h following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Bronchoalveolar lavage fluid analysis revealed increased total protein, and lung histology revealed increased cellular inflammation following IRI, but not BNx, compared with sham controls. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n ϭ 3/group), which were analyzed by robust multichip average and significance analysis of microarrays and linked to gene ontology (GO) terms using MAPPFinder. The microarray power analysis predicted that the false discovery rate (q Ͻ 1%) and Ն50%-fold change compared with sham would represent significant changes in gene expression. Analysis identified 266 and 455 ischemia-specific, AKI-associated lung genes with increased expression and 615 and 204 with decreased expression at 6 and 36 h, respectively, compared with sham controls. Real-time PCR analysis validated select array changes in lung serum amyloid A3 and endothelin-1. GO analysis revealed significant activation (Z Ͼ 1.95) of several proinflammatory and proapoptotic biological processes. Ischemic AKI induces functional and transcriptional changes in the lung distinct from those induced by uremia alone. Further investigation using this lung molecular signature induced by kidney IRI will provide mechanistic insights and new therapies for critically ill patients with AKI.ischemia-reperfusion; lung injury; microarray ISCHEMIC ACUTE KIDNEY INJURY (AKI) occurs in various clinical settings including shock, sepsis, transplantation, and vascular surgery. Despite advances in renal replacement therapy, the mortality of patients with AKI has remained high over the past few decades, and renal insufficiency continues to be a sensitive marker for a poor outcome in critically ill patients (2, 22). Epidemiological studies have identified an association between AKI and dysfunction of extrarenal organs (4). Given the persistent AKI-associated poor clinical outcomes, there is a need to study the systemic and remote organ effects that occur in the context of AKI.Acute lung injury (ALI) is a significant cause of respiratory failure in the intensive care unit and carries a substantial mortality of 30 -40% (8). When combined with AKI, mortality approaches 80% (26). The clinical presentation of AKI-associate...

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“…Work from the Deitch lab [1,7,[15][16][17][18][19] as well as work from our group [4,5,8,20,21] has confirmed that PSML is the mechanistic link between gut I/R and MOF.…”

Section: Discussionmentioning

confidence: 78%

“…[5] This is also congruent with prior work in HUVECs demonstrating the greatest decrease in cell viability after application of 2 nd and 3 rd hour of PSML. [17] Of interest, combining samples of PSML from each hour has greater bioactivity than any single time point alone. This suggests that there are different mediators acting as the primary inflammatory signal at different time point.…”

Section: Discussionmentioning

confidence: 99%

Postshock Mesenteric Lymph Induces Endothelial NF-κB Activation

Damle

Moore

Nydam

et al. 2007

Journal of Surgical Research

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Background-Post-hemorrhagic shock mesenteric lymph (PSML) has been shown to activate pulmonary endothelial cells, and cause lung injury. Although multiple mediators may be involved, most of these effects are mediated by NF-κB activation. Degradation of the inhibitor of kappa B (IκB) is a key regulatory step in the activation of NF-κB. We therefore hypothesized that PSML would cause IκB degradation with subsequent NF-κB phosphorylation and nuclear translocation.

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A study of the biologic activity of trauma-hemorrhagic shock mesenteric lymph over time and the relative role of cytokines

Cited by 73 publications

References 19 publications

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Gelsolin is Depleted in Post-Shock Mesenteric Lymph

Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy

Postshock Mesenteric Lymph Induces Endothelial NF-κB Activation

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