Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah I Toxin from Scorpion Venom

International audienceBradykinins are released from kininogen by kallikrein. They increase capillary lung permeability after their binding to β1 and especially β2 receptors before being metabolized by kininase enzyme. This study was performed to evaluate cardiopulmonary damages and inflammatory response on injected rats with Aah I toxin of scorpion venom and the involvement of Kallikrein-Kinin system in this pathogenesis. Obtained results revealed that Aah I toxin induces inflammatory cell infiltration accompanied by cellular peroxidase activities, a release of cytokine levels, pulmonary and myocardial damage, with altered metabolic activities and imbalanced redox status. Administration of aprotinin (bradykinin inhibitor) and especially icatibant (bradykinin β2 receptor antagonist) seemed to be able to protect animals against the toxicity of Aah I; nevertheless, the use of captopril (kininase II inhibitor) reduced partially some cardiac disorders. These findings indicate that the kallikrein-kinin system may contribute to the physiopathological effect and lung edema formation induced by toxin, which suggests a potential use of drugs with significant anti-kinin properties

Epithelial decision makers:In search of the 'epimmunome'

Frequent microbial and non-microbial challenges to epithelial cells trigger discrete pathways, promoting molecular changes, such as the secretion of specific cytokines and chemokines, and alterations to molecules displayed at the epithelial cell surface. In combination, these molecules impose major decisions on innate and adaptive immune cells. Depending on context, those decisions can be as diverse as those imposed by professional antigen presenting cells, benefitting the host by balancing immune competence with the avoidance of immunopathology. Nonetheless, this potency of epithelial cells is also consistent with the causal contribution of epithelial dysregulation to myriad inflammatory diseases. This pathogenic axis provides an attractive target for tissue-specific clinical manipulation. In this context, a research goal should be to identify all molecules used by epithelial cells to instruct immune cells. We term this the epimmunome

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission