Allostatic stress load and CMV serostatus impact immune response to maximal exercise in collegiate swimmers.

Collegiate athletes are exposed to varying levels of academic and physical stressors, placing them at increased risk for stress-activated latent viral infections. However, the impact of allostatic stress load on the immune response to maximal exercise in athletes remains largely unknown. This study examined the effects of a 7-mo training period and cytomegalovirus (CMV) serostatus on immune cell response to high-intensity swim tests within a group of collegiate swimmers. Samples were collected from 15 National Collegiate Athletic Association Division I swimmers (9 men, 6 women: 19.87 ± 0.64 yr) before and after exhaustive in-pool swims at 2 time points (V1: immediately post-season 1 and V3: beginning of season 2). An additional off-season (V2) time point was collected in a subset of 9 swimmers. Natural killer (NK) cell, B cell, and T cells were quantified by flow cytometry. Linear mixed models were used to determine the effects of exercise, time point, and CMV serostatus (α = 0.05). Resting senescent CD8+ T cells were higher in CMV-seropositive participants at V3 (P = 0.005). CMV-seronegative participants had a decrease in resting senescent CD8+ T cells from V1 to V3 (P = 0.021). After acute exercise, CMV-seropositive participants had lower naïve CD8+ T cells (P < 0.001) and higher senescent CD8+ T cells (P < 0.001). Increased cumulative stress levels did not appear to affect B-cell and NK-cell compartments. Immune response to exercise was impacted by CMV serostatus and allostatic stress load. Young CMV-seropositive athletes exposed to elevated stressors should be monitored to determine long-term effects of training and academic stressors.NEW & NOTEWORTHY Allostatic stress load is associated with impaired immune response to maximal exercise in cytomegalovirus (CMV)-seropositive subjects but not in CMV-seronegative young healthy adults.

Catabolism of 4-hydroxy-2-trans-nonenal by THP1 monocytes/macrophages and inactivation of carboxylesterases by this lipid electrophile.

Oxidative stress in cells and tissues leads to the formation of an assortment of lipid electrophiles, such as the quantitatively important 4-hydroxy-2-trans-nonenal (HNE). Although this cytotoxic aldehyde is atherogenic the mechanisms involved are unclear. We hypothesize that elevated HNE levels can directly inactivate esterase and lipase activities in macrophages via protein adduction, thus generating a biochemical lesion that accelerates foam cell formation and subsequent atherosclerosis. In the present study we examined the effects of HNE treatment on esterase and lipase activities in human THP1 monocytes/macrophages at various physiological scales (i.e., pure recombinant enzymes, cell lysate, and intact living cells). The hydrolytic activities of bacterial and human carboxylesterase enzymes (pnbCE and CES1, respectively) were inactivated by HNE in vitro in a time- and concentration-dependent manner. In addition, so were the hydrolytic activities of THP1 cell lysates and intact THP1 monocytes and macrophages. A single lysine residue (Lys105) in recombinant CES1 was modified by HNE via a Michael addition reaction, whereas the lone reduced cysteine residue (Cys389) was found unmodified. The lipolytic activity of cell lysates and intact cells was more sensitive to the inhibitory effects of HNE than the esterolytic activity. Moreover, immunoblotting analysis using HNE antibodies confirmed that several cellular proteins were adducted by HNE following treatment of intact THP1 monocytes, albeit at relatively high HNE concentrations (>50µM). Unexpectedly, in contrast to CES1, the treatment of a recombinant human CES2 with HNE enhanced its enzymatic activity ∼3-fold compared to untreated enzyme. In addition, THP1 monocytes/macrophages can efficiently metabolize HNE, and glutathione conjugation of HNE is responsible for ∼43% of its catabolism. The functional importance of HNE-mediated inactivation of cellular hydrolytic enzymes with respect to atherogenesis remains obscure, although this study has taken a first step toward addressing this important issue by examining the potential of HNE to inhibit this biochemical activity in a human monocyte/macrophage cell line.