Clinical analysis of selected complement-derived molecules in human adipose tissue

Abstract

BackgroundIt has been suggested that action of complement cascade [CC]-derived anaphylatoxins/molecules may represent a missing link between obesity and metabolic disorders. However, to date, the direct biochemical/immunomodulatory composition of the human AT environment remains poorly understood. In this study, we examined plasma and AT (subcutaneous and visceral/omental) levels of selected CC-derived anaphylatoxins/molecules, and adipsin as well as verified their associations with immune and stem cells chemoattractant - stromal-derived factor-1 (SDF-1).MethodsA total of 70 (35 subcutaneous and 35 omental) AT samples were obtained from patients undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of C3a, C5a, C5b-9/membrane attack complex (MAC), complement factor D (adipsin) were measured using ELISA.ResultsAT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases P < 0.0000001). Moreover, in subcutaneous AT, robust C3a and adipsin concentrations were observed, whereas high levels of C5b-9/MAC were detected in the visceral depots. In addition, we established the correlations between analyzed molecular substances and body composition, BMI and/or the adiposity index of the examined patients.ConclusionsOur study demonstrated for the first time that significantly reduced levels of complement-derived molecules were present in human AT than in the peripheral blood, and that these factors are associated with the metabolic status of examined individuals. Moreover, in human AT, various associations between complement-derived molecules and SDF-1 levels exist.

Adipokines: a link between obesity and dementia?

“…77 There are no observational human studies showing an association between adipsin and dementia. However, it is interesting to note that adipsin is elevated in animal models that have been treated with functional gamma secretase inhibitors.…”

Estrogenic Steroid Hormones in Lung Cancer

“…A phase I clinical trial is underway that will evaluate side effects and best dose of the irreversible steroidal aromatase inhibitor exemestane in combination with chemotherapy for late stage lung cancer therapy (NCT01664754). Other enzymes involved in intratumoral production and metabolism of estrogens are also under investigation as potential targets for lung cancer therapy 48 .…”

Engineering Stem Cells for Biomedical Applications

“…[253] In particular, various experimental models have previously validated the use of MV and phase I clinical trials are in progress to evaluate the safety and maximal tolerated dose of oncolytic MV for cancers such as ovarian cancer, myeloma, and glioma. [254] To further improve viral delivery to the tumor, the authors infected patient-derived MSCs with MV via centrifugation (70% infectivity with 1000 × g centrifugation for 5–10 minutes), which did not compromise cell viability.…”