Natural killer cells as biomarkers of hyperbaric stress during a dry heliox saturation dive.
ABSTRACT Diving, hyperbaric oxygen, and decompression have been described as inducers of alterations in various components of the human immune system, such as the distribution of circulating lymphocytes. Hypothetically, the monitoring of specific lymphocyte subsets during hyperbaric exposure, including T- and NK-cell subsets, can serve as biomarkers of hyperbaric stress.
Eight experienced saturation divers and eight reference subjects, naive to deep saturation diving, were examined. Peripheral blood mononuclear cells were isolated before and at different points during a 19.3-d dry heliox saturation dive to 2.64 MPa (254 msw). The NK cell cytotoxicity was estimated in a 4-h 51Cr-release assay using the NK cell sensitive tumor cell-line K562 as target cells. The major lymphocyte subpopulations, with special emphasis on the NK cell subsets, were phenotypically delineated by the use of 4-color flow cytometry.
Although NK cell cytotoxicity increased significantly in the divers during the compression phase and the reference subjects who remained in normoxic conditions outside the chamber, the NK cell cytotoxicity was significantly higher in the divers.
This finding, together with augmentation in the absolute number of circulating NK cells in the divers due to a possible activation of specific parts of the innate cellular immune system during hyperbaric exposure, suggests the monitoring of specific immune functions can be useful as biomarkers of hyperbaric-induced inflammatory stress.
- SourceAvailable from: Jiuping Ji[Show abstract] [Hide abstract]
ABSTRACT: Exposure to oxygen-rich environments can lead to oxidative damage, increased body iron stores, and changes in status of some vitamins, including folate. Assessing the type of oxidative damage in these environments and determining its relationships with changes in folate status are important for defining nutrient requirements and designing countermeasures to mitigate these effects. Responses of humans to oxidative stressors were examined in participants undergoing a saturation dive in an environment with increased partial pressure of oxygen, a NASA Extreme Environment Mission Operations mission. Six participants completed a 13-d saturation dive in a habitat 19 m below the ocean surface near Key Largo, FL. Fasting blood samples were collected before, twice during, and twice after the dive and analyzed for biochemical markers of iron status, oxidative damage, and vitamin status. Body iron stores and ferritin increased during the dive (P<0.001), with a concomitant decrease in RBC folate (P<0.001) and superoxide dismutase activity (P<0.001). Folate status was correlated with serum ferritin (Pearson r = -0.34, P<0.05). Peripheral blood mononuclear cell poly(ADP-ribose) increased during the dive and the increase was significant by the end of the dive (P<0.001); γ-H2AX did not change during the mission. Together, the data provide evidence that when body iron stores were elevated in a hyperoxic environment, a DNA damage repair response occurred in peripheral blood mononuclear cells, but double-stranded DNA damage did not. In addition, folate status decreases quickly in this environment, and this study provides evidence that folate requirements may be greater when body iron stores and DNA damage repair responses are elevated.PLoS ONE 01/2012; 7(2):e31058. · 3.53 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: During scuba diving, the circulatory system is stressed by an elevated partial pressure of oxygen while the diver is submerged and by decompression-induced gas bubbles on ascent to the surface. This diving-induced stress may trigger decompression illness, but the majority of dives are asymptomatic. In this study we have mapped divers' blood transcriptomes with the aim of identifying genes, biological pathways and cell types perturbed by the physiological stress in asymptomatic scuba diving. Ten experienced divers abstained from diving for more than two weeks before performing a three-day series of daily dives to 18 meters depth for 47 minutes while breathing compressed air. Blood for microarray analysis was collected before and immediately after the first and last dives, and ten matched non-divers provided controls for pre-dive stationary transcriptomes. MetaCore GeneGo analysis of the pre-dive samples identified stationary upregulation of genes associated with apoptosis, inflammation and innate immune responses in the divers, most significantly involving genes in the TNFR1 pathway of caspase-dependent apoptosis, HSP60/HSP70 signaling via TLR4 and NF-κB-mediated transcription. Diving caused pronounced shifts in transcription patterns characteristic of specific leukocytes, with downregulation of genes expressed by CD8+ T lymphocytes and NK cells and upregulation of genes expressed by neutrophils, monocytes and macrophages. Antioxidant genes were upregulated. Similar transient responses were observed after the first and last dive. The results indicate that sub-lethal oxidative stress elicits the myeloid innate immune system in scuba diving, and that extensive diving may cause persistent change in pathways controlling apoptosis, inflammation and innate immune responses.Physiological Genomics 08/2013; · 2.81 Impact Factor