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31.
Differences in maintenance of CD8+ and CD4+ bacteria-specific effector-memory T cell populations 总被引:1,自引:0,他引:1
Schiemann M Busch V Linkemann K Huster KM Busch DH 《European journal of immunology》2003,33(10):2875-2885
Our knowledge about the kinetics and dynamics of complex pathogen-specific CD8(+) T cell responses and the in vivo development of CD8(+) memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4(+) T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8(+) and CD4(+) T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteria-specific CD8(+) and CD4(+) T cells during the effector and post-effector phases are synchronized. However, later during the memory phase, CD8(+) and CD4(+) T cell populations differ substantially. Whereas CD8(+) memory T cell populations with immediate effector function are readily detectable in lymphoid and non-lymphoid tissues and remain remarkably stable in size, antigen-specific CD4(+) effector-memory T cells decline continuously in frequency over time. These findings have important implications for the better understanding of the in vivo development of protective immunity towards intracellular pathogens. 相似文献
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33.
Finn Jung Katharina Burger Raphaela Staltner Annette Brandt Sebastian Mueller Ina Bergheim 《Nutrients》2021,13(5)
Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients. 相似文献
34.
Katharina Voigt Emily Giddens Romana Stark Emma Frisch Neda Moskovsky Naomi Kakoschke Julie C. Stout Mark A. Bellgrove Zane B. Andrews Antonio Verdejo-Garcia 《Nutrients》2021,13(6)
Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours. 相似文献
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36.
Carolin Lepa Sascha Hoppe Antje Stber Boris V. Skryabin Laura Katharina Sievers Barbara Heitplatz Giuliano Ciarimboli Ute Neugebauer Maja T. Lindenmeyer Clemens D. Cohen Hannes C.A. Drexler Peter Boor Thomas Weide Hermann Pavenstdt Britta George 《Journal of the American Society of Nephrology : JASN》2021,32(2):357
BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes. 相似文献
37.
Tarek Debs Niccolo Petrucciani Sebastian Frey Carine Korkmaz Katharina Hufschmidt Eric Sejor Houssam Eddine Bitar Imed Ben Amor Antonio Iannelli Jean Gugenheim 《Surgery for obesity and related diseases》2021,17(5):901-908
BackgroundBariatric surgery has become widely performed for treating patients with morbid obesity, and the age limits are being pushed further and further as the procedure proves safe. After massive weight loss, many of those patients seek body-contouring surgery for excess skin and fat.ObjectivesTo analyze the feasibility and the safety of abdominoplasty in patients older than 55 years old after bariatric surgery.SettingUniversity hospital medical center.MethodsWe performed a retrospective review of prospectively collected data from patients aged older than 55 years who had undergone abdominoplasty following massive weight loss due to a bariatric surgery at a single institution from 2004 to 2017. The data analyzed included age, gender, preoperative body mass index, associated interventions, co-morbidities, and postoperative complications.ResultsWe retrieved records for 104 patients; 85.6% percent of them were female, and the mean age was 60.1 ± 3.9 years old. Of the 104 patients, 21 (20.2%) underwent a sleeve gastrectomy and 77 (74%) underwent a Roux-en-Y gastric bypass. The mean interval between the bariatric surgery and the abdominoplasty was 33.6 ± 26.9 months. The mean preoperative weight and body mass index were 76.1 ± 14.5 kg and 28.9 ± 4.5 kg/m2, respectively. A total complication rate of 20% was observed. The only factor significantly associated with postoperative morbidity was the associated procedure (P = .03), when we performed another procedure at the same time as the abdominoplasty. Complications included postoperative bleeding in 5 patients (4.8%), seromas in 5 patients (4.8%), surgical site infections in 12 patients (11.5%), and wound dehiscence or ischemia in 2 patients (1.9%). No mortality occurred.ConclusionAbdominoplasty can be safely performed in carefully selected patients older than 55 years old after weight loss surgery, and does not present increased morbidity or mortality. We recommend that surgeons avoid adding concomitant procedures when possible, to decrease the risk of complications. It is also important to look at the patient’s previous maximum BMI levels, as a higher maximum BMI can predict higher postoperative risks and longer hospital stays. 相似文献
38.
Sushmita Chakraborty Jakob Schneider Dipendra Kumar Mitra Katharina F. Kubatzky 《Immunology》2023,169(3):309-322
Interleukin (IL)-9 is an emerging player in the pathogenesis of various chronic inflammatory diseases including bone disorders like rheumatoid arthritis (RA) and psoriatic arthritis. Recently, IL-9 was shown to enhance the osteoclast formation and their function in RA. However, the mechanisms by which IL-9 influences osteoclastogenesis are not known. Therefore, in this study we aimed to unravel the direct and indirect ways by which IL-9 can influence osteoclast formation. We used mouse bone marrow precursor cells for checking the effect of IL-9 on osteoclast differentiation and its function. Next, IL-9 induced signalling pathway were checked in the process of osteoclastogenesis. T cells play an important role in enhancing osteoclastogenesis in inflammatory conditions. We used splenic T cells to understand the impact of IL-9 on the functions of T effector (Teff) and regulatory T (Treg) cells. Furthermore, the effect of IL-9 mediated modulation of the T cell response on osteoclasts was checked using a coculture model of T cells with osteoclast precursors. We showed that IL-9 enhanced osteoclast formation and its function. We found that IL-9 activates STAT3, P38 MAPK, ERK1/2, NFκB and we hypothesize that it mediates the effect on osteoclastogenesis by accelerating mitochondrial biogenesis. Additionally, IL-9 was observed to facilitate the functions of pro-osteoclastogenic IL-17 producing T cells, but inhibits the function of anti-osteoclastogenic Treg cells. Our observations suggest that IL-9 can influence osteoclastogenesis directly by modulating the signalling cascade in the precursor cells; indirectly by enhancing IL-17 producing T cells and by reducing the functions of Treg cells. 相似文献
39.
Stefan Silbernagl Katharina Völker William H. Dantzler 《Pflügers Archiv : European journal of physiology》1994,429(2):210-215
To investigate the fluxes of cationic amino acids beyond the proximal convolution, we micropunctured and microperfused superficial tubules of male Wistar rats in vivo et situ. In free-flow micropuncture experiments, the concentrations of endogenous L-arginine+, [Arg], and of intravenously infused L-homoarginine+, [HoArg], were determined by HPLC. Fluorescein isothiocyanatelabeled inulin was detected on-line in the same tubular fluid samples. To determine undirectional fluxes, radiolabeled Arg and inulin were (1) microperfused through short loops of Henle and (2) microinfused into different tubule segments to measure urinary recovery of the radiolabel. At a mean [Arg]plasma of 116 mol/l, [Arg] was 9.3 mol/l in the late proximal tubule (LPT), and 35.6 mol/l in the early distal tubule (EDT) corresponding to fractional deliveries (FD) of 0.055 in LPT and 0.078 in EDT. Fractional urinary excretion (FE) of Arg was 0.00033 (P<0.05 vs FDEDT). Infusion of HoArg (2.5 or 7.5 mol/min) led to respective mean [HoArg]plasma values of 1.44 and 3.73 mmol/l, and resulted in respective FDLPT values for HoArg of 0.23 and 0.53, respective FDEDT values of 0.29 and 0.41, and finally, respective FE values for HoArg of 0.25 and 0.58. When short loops of Henle were microperfused with 1 or 50 mmol/l [14C]Arg (+[3H]inulin), fractional recovery (FR) of 14C (relative to inulin) in the EDT was 0.13 and 0.36, respectively. During microinfusion of radiolabeled Arg (1 or 50 mmol/l) and inulin into LPT, the urinary FR of the radiolabel was 0.14, or 0.59, respectively. If 0.007, 1 or 50 mmol/l radiolabeled Arg were microinfused into EDT, the respective urinary FR of the radioactivity was 1.02, 1.10, or 1.01. Microperfusion of microinfusion of 1 mmol/l [14C]Arg plus 50 mmol/l HoArg resulted in a FREDT of 14C of 0.43 (loop, perfusion) and an FE for 14C of 0.69. Five conclusions can be drawn. First, cationic amino acids can enter and leave the lumen of short loops of Henle through specific carrier(s) at high rates, although, secondly, net transport is small or absent. Thus, medullary tubule cells can be supplied with Arg from the lumen of short loops of Henle for urea and nitric oxide production. Thirdly, the distal convolution of superficial nephrons and the collecting duct are not permeable to Arg. Thus, fourthly, the difference between FDEDT and urinary FE of Arg must be explained by an inter-nephron heterogeneity between deep and superficial nephrons. Finally, the process responsible for the different Arg handling in deep nephrons is not accessible to HoArg or, if so, it is saturated at millimolar concentrations. 相似文献
40.
Katharina Wenzel-Seifert Jürgen Ervens Roland Seifert 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(4):396-402
Summary The chemoattractants, N-formyl-L-methio-nyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), complement C5a and platelet-activating factor (PAF), induce ß-glucuronidase release and aggregation and an increase in cytosolic Ca2+ [Ca2+]i in human neutrophils. We studied the roles of cAMP and cGMP in neutrophil avtivation, using their cell-permeant analogues, N6,2-O-dibutyryl adenosine 3:5-cyclic monophosphate (Bt2cAMP) and N2 ,2-O-dibutyryl guanosine 3:5-cyclic monophosphate (Bt2cGMP) and the NO-containing compounds, sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1) and its prodrug, molsidomine (SIN-10). Bt2cAMP, Bt2cGMP, SIN-1 and SIN-10 but not SNP inhibited exocytosis induced by fMet-Leu-Phe. Superoxide dismutase potentiated the inhibitory effect of SIN-1. Bt2cGMP and SNP potentiated C5a-induced ß-glucuronidase release, Bt2cAMP, KCN, SIN-1 and SIN-10 being ineffective. KCN partially reversed the stimulatory effect of SNP, and in the presence of superoxide dismutase, SIN-1 potentiated C5a-induced exocytosis. PAF-induced ß-glucuronidase release was not affected by Bt2cAMP, Bt2cGMP, SNP and SIN-1. Bt2cGMP was more effective than Bt2cAMP to inhibit aggregation and the increase in [Ca2+]i induced by fet-Leu-Phe at submaximally effective concentrations. C5a-induced rises in [Ca2+]i were not affected by Bt2cAMP and Bt2cGMP. Bt2cAMP but not Bt2cGMP inhibited the effect of PAF at submaximally effective concentrations on [Ca2+]i. Our data suggest (I) that Bt2cGMP and Bt2cAMP differentially modulate neutrophil activation, that (II) NO-containing compounds partially mimick the effects of Bt2cGMP on exocytosis and that (III) cGMP plays an inhibitory role in fMet-Leu-Phe- and a stimulatory role in C5a-induced ß-glucuronidase release.
Send offprint requests to R. Seifert at the above address 相似文献