Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathogenic inflammation and immune suppression are the cardinal features that underlie the pathogenesis of severe systemic inflammatory syndrome and sepsis. Neutrophil exhaustion may play a key role during the establishment of pathogenic inflammation and immune suppression through elevated expression of inflammatory adhesion molecules such as ICAM1 and CD11b as well as immune-suppressors such as PD-L1. However, the mechanism of neutrophil exhaustion is not well understood. We demonstrated that murine primary neutrophils cultured in vitro with the prolonged lipopolysaccharides (LPS) stimulation can effectively develop an exhaustive phenotype resembling human septic neutrophils with elevated expression of ICAM1, CD11b, PD-L1 as well as enhanced swarming and aggregation. Mechanistically, we observed that TICAM2 is involved in the generation of neutrophil exhaustion, as TICAM2 deficient neutrophils have the decreased expression of ICAM1, CD11b, PD-L1, and the reduced aggregation following the prolonged LPS challenge as compared to wild type (WT) neutrophils. LPS drives neutrophil exhaustion through TICAM2 mediated activation of Src family kinases (SFK) and STAT1, as the application of SFK inhibitor Dasatinib blocks neutrophil exhaustion triggered by the prolonged LPS challenge. Functionally, TICAM2 deficient mice were protected from developing severe systemic inflammation and multi-organ injury following the chemical-induced mucosal damage. Together, our data defined a key role of TICAM2 in facilitating neutrophil exhaustion and that targeting TICAM2 may be a potential approach to treating the severe systemic inflammation.
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PMID:TICAM2-related pathway mediates neutrophil exhaustion. 3287 53

Chronic immune activation and inflammation are unwanted consequences of many pathological conditions, since they could lead to tissue damage and immune exhaustion, both of which can worsen the pathological condition status. In fact, the immune system is naturally equipped with immunoregulatory cells that can limit immune activation and inflammation. However, chronic activation of downregulatory immune responses is also associated with unwanted consequences that, in turn, could lead to disease progression as seen in the case of cancer and chronic infections. Myeloid-derived suppressor cells (MDSCs) are now considered to play a pivotal role in the pathogenesis of different inflammatory pathological conditions, including different types of cancer and chronic infections. As a potent immunosuppressor cell population, MDSCs can inhibit specific and non-specific immune responses via different mechanisms that, in turn, lead to disease persistence. One such mechanism by which MDSCs can activate their immunosuppressive effects is accomplished by secreting copious amounts of immunosuppressant molecules such as interleukin-10 (IL-10). In this article, we will focus on the pathological role of MDSC expansion in chronic inflammatory conditions including cancer, sepsis/infection, autoimmunity, asthma and ageing, as well as some of the mechanisms by which MDSCs/IL-10 contribute to the disease progression in such conditions.
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PMID:Mechanisms of immune suppression by myeloid-derived suppressor cells: the role of interleukin-10 as a key immunoregulatory cytokine. 3293 21

In conditions of abdominal sepsis with indications of first- or second-stage shock, blood cells undergo significant ultrastructural changes that cause impaired gas exchange, changes in reactivity, and decompensation of organs and systems functions. This paper presents a cross-sectional prospective study aimed at researching the ultrastructure of blood cells in children experiencing abdominal septic shock against the background of generalized purulent peritonitis of appendicular origin. This study was conducted with 15 children aged 6-12 who were undergoing treatment for generalized appendicular purulent peritonitis, with first- or second-stage abdominal septic shock, in emergency care. The changes in the ultrastructure of erythrocytes did not correspond to changes characteristic of eryptosis, which confirms their occurrence under the influence of such pathogenic factors as intoxication, metabolic, water-electrolyte balance, and acid-base disorders. Ultrastructural changes of granulocytes indicate their hyperactivation, which leads to the exhaustion of membrane synthetic resources, membrane destruction, ineffective expenditure of bactericidal factors on substrates that are not subject to destruction. In lymphocytes, disorganization of the nuclear membrane and intracellular membranes, uneven distribution of chromatin, the hypertrophied Golgi apparatus, and a large number of young mitochondria, lysosomes, ribosomes, vesicles manifesting the disruption of metabolism, stress and decompensation of energy supply and protein synthesis systems, have been demonstrated. In conditions of abdominal sepsis with indications of first- or second-stage shock, blood cells undergo substantial ultrastructural changes causing gas exchange disruption, changes in reactivity, as well as decompensation of organs and system functioning.
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PMID:Ultrastructural Changes of Blood Cells in Children with Generalized Purulent Peritonitis: A Cross-Sectional and Prospective Study. 3308 Aug 60


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