Modulations of Neuroendocrine Stress Responses During Confinement in Antarctica and the Role of Hypobaric Hypoxia

The Antarctic continent is an environment of extreme conditions. Only few research stations exist that are occupied throughout the year. The German station Neumayer III and the French-Italian Concordia station are such research platforms and human outposts. The seasonal shifts of complete daylight (summer) to complete darkness (winter) as well as massive changes in outside temperatures (down to -80 degrees C at Concordia) during winter result in complete confinement of the crews from the outside world. In addition, the crew at Concordia is subjected to hypobaric hypoxia of similar to 650 hPa as the station is situated at high altitude (3,233 m). We studied three expedition crews at Neumayer Ill (sea level) (n = 16) and two at Concordia (high altitude) (n = 15) to determine the effects of hypobaric hypoxia on hormonal/metabolic stress parameters [endocannabinoids (ECs), catecholamines, and glucocorticoids] and evaluated the psychological stress over a period of 11 months including winter confinement. In the Neumayer III (sea level) crew, EC and n-acylethanolamide (NAE) concentrations increased significantly already at the beginning of the deployment (p < 0.001) whereas catecholamines and cortisol remained unaffected. Over the year, ECs and NAEs stayed elevated and fluctuated before slowly decreasing till the end of the deployment. The classical stress hormones showed small increases in the last third of deployment. By contrast, at Concordia (high altitude), norepinephrine concentrations increased significantly at the beginning (p < 0.001) which was paralleled by low EC levels. Prior to the second half of deployment, norepinephrine declined constantly to end on a low plateau level, whereas then the EC concentrations increased significantly in this second period during the overwintering (p < 0.001). Psychometric data showed no significant changes in the crews at either station. These findings demonstrate that exposition of healthy humans to the physically challenging extreme environment of Antarctica (i) has a distinct modulating effect on stress responses. Additionally, (ii) acute high altitude/hypobaric hypoxia at the beginning seem to trigger catecholamine release that downregulates the EC response. These results (iii) are not associated with psychological stress

Multimer formation and ligand recognition by the long pentraxin PTX3 - Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component

PTX3 is a prototypic long pentraxin consisting of a C-terminal 203- amino acid pentraxin-like domain coupled with an N-terminal 178-amino acid unrelated portion. The present study was designed to characterize the structure and ligand binding properties of human PTX3, in comparison with the classical pentraxins C-reactive protein and serum amyloid P component. Sequencing of Chinese hamster ovary cell-expressed PTX3 revealed that the mature secreted protein starts at residue 18 (Glu). Lectin binding and treatment with N-glycosidase F showed that PTX3 is N-glycosylated, sugars accounting for 5 kDa of the monomer mass (45 kDa). Circular dichroism analysis indicated that the protein consists predominantly of \u3b2-sheets with a minor \u3b1-helical component. While in gel filtration the protein is eluted with a molecular mass of 43900 kDa, gel electrophoresis using nondenaturing, nonreducing conditions revealed that PTX3 forms multimers predominantly of 440 kDa apparent molecular mass, corresponding to decamers, and that disulfide bonds are required for multimer formation. The ligand binding properties of PTX3 were then examined. As predicted based on modeling, inductive coupled plasma/atomic emission spectroscopy showed that PTX3 does not have coordinated Ca2+. Unlike the classical pentraxins CRP and SAP. PTX3 did not bind phosphoethanolamine, phosphocholine, or high pyruvate agarose. PTX3 in solution, bound to immobilized C1q, but not C1s, and, reciprocally, C1q bound to immobilized PTX3. Binding of PTX3 to C1q is specific and saturable with a K(d) 7.4 x 10-8 M as determined by solid phase binding assay. The Chinese hamster ovary cell-expressed pentraxin domain bound C1q when multimerized. Thus, as predicted on the basis of computer modeling, the prototypic long pentraxin PTX3 forms multimers, which differ from those formed by classical pentraxins in terms of protomer composition and requirement for disulfide bonds, and does not recognize CRP/SAP ligands. The capacity to bind C1q, mediated by the pentraxin domain, is consistent with the view that PTX3, produced in tissues by endothelial cells or macrophages in response to interleukin-1 and tumor necrosis factor, may act as a local regulator of innate immunity