Platelets mediate cytotoxic T lymphocyte-induced liver damage.
Ontology highlight
ABSTRACT:
SUBMITTER: Iannacone M
PROVIDER: S-EPMC2908083 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ALI is one of the most common disease processes in adult and pediatric intensive care units and results in significant morbidity and mortality. The pathophysiology of ALI begins with a massive pro-inflammatory response likely mediated by as yet uncharacterized platelet/endothelium interactions with macrophage activation. This leads to a cytokine/chemokine cascade producing endothelial disruption. Neutrophilic infiltration of the alveolar wall and alveolar space with a concomitant procoagulant state develops. Despite the fact that inadequate understanding of ALI pathophysiology remains a barrier to effective treatment, novel therapeutics including ventilatory manipulations and anti-inflammatory molecules are beginning to improve the morbidity and mortality associated with this disease process. Experiment Overall Design: Acute Lung Injury (ALI) represents a spectrum of critical pulmonary illness in which inflammatory processes lead to varying degrees of alveolar damage and respiratory failure. ALI is a common disease process in the intensive care unit (ICU) with high morbidity and mortality. Based on new insights into the molecular processes of lung injury, we hypothesize that a temporal analysis of cells of innate immunity and thrombosis will demonstrate changes in mRNA and protein expression that are significantly associated with progression of ALI. Additionally, the analysis of the resulting datasets will lead to an unprecedented understanding of the pathogenesis of ALI.
2008-06-11 | E-GEOD-10361 | biostudies-arrayexpress
Project description:ALI is one of the most common disease processes in adult and pediatric intensive care units and results in significant morbidity and mortality. The pathophysiology of ALI begins with a massive pro-inflammatory response likely mediated by as yet uncharacterized platelet/endothelium interactions with macrophage activation. This leads to a cytokine/chemokine cascade producing endothelial disruption. Neutrophilic infiltration of the alveolar wall and alveolar space with a concomitant procoagulant state develops. Despite the fact that inadequate understanding of ALI pathophysiology remains a barrier to effective treatment, novel therapeutics including ventilatory manipulations and anti-inflammatory molecules are beginning to improve the morbidity and mortality associated with this disease process. Keywords: Time Series Design, ALI - acute lung injury, ARDS - acute respiratory distress syndrome
2008-02-02 | GSE10361 | GEO
Project description:Platelets are classically known for their roles in bleeding control and occlusive thrombus formation causing ischaemic tissue damage. Recently non-classical roles for platelets have been described, many of which may be mediated by the heterogeneous cargo that platelets secrete from granular stores upon activation. Using an in vitro model of ischaemic injury to ventricular cardiomyocytes, we observed that platelets, through secreted factors, delayed the rate of cardiomyocyte death during ischaemia. This protective effect appeared independent of platelet dense granule cargo, but required α-granule components stromal cell-derived factor (SDF)-1α and transforming growth factor (TGF) β1. Protein kinase C (PKC) activity within cardiomyocytes was responsible for mediating the protective signals initiated by the released platelet cargo. Importantly, pretreating platelets with a P2Y12 antagonist, but not the cyclooxygenase inhibitor aspirin, substantially attenuated this protective effect. These findings therefore reveal a paradoxically protective role for platelet activation during cardiac ischaemia and could have important implications for the use of anti-platelet therapeutics in the management of myocardial infarction.
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