Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

Abstract

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania^®, STRING^®, and Perseus^® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis.

Keywords: airline; hypobaric hypoxia; immune response; pressure chamber.

Figure 1

Pressure profile of the measurement: X-axis, time in min; Y-axis, pressure change in kPa. Phase 1 (red line): decompression phase; Phase 2 (blue line): isopression phase; Phase 3 (green line): compression phase.

Figure 2

Proteins identified as significantly regulated two-dimensional gel electrophoresis (2-DIGE) and bioinformatic analysis. Red = upregulated; green = downregulated.

Figure 3

GeneMania^® network by the original dataset. Evidence shows four functions: regulation of haemostasis, platelet activation, humoral immune response, and B cell mediated immunity.

Figure 4

Categorical Cluster analysis (heat map) by Perseus^®. The rows show the names of the proteins altered in the 12 spots. The columns show the timing groups of the experiment (before and after hypobaric hypoxia, each blood sample was obtained twice for each subject). An intensity colour scale to interpret the relative quantities from the heat map is shown.

Figure 5

Categories of biological processes, cellular components, and molecular functions as identified by WebGestalt (Available online: http://genereg.ornl.gov/webgestalt/). The GO Slim summary is based upon the nine unique Entrez Gene IDs. Among the nine unique Entrez Gene IDs, nine IDs are annotated to the selected functional categories and also in the reference gene list, which are used for the enrichment analysis. Biological Process, Cellular Component and Molecular Function categories are represented by red, blue and green bars, respectively. The height of the bar represents the number of user list genes observed in the category.

Figure 6

Haemostasis pathway fibrin clotting gathered by the website (available online: www.reactome.org). Platelet activation and formation of the fibrin clot are affected by the proteins found in the present study