Noradrenaline and its end metabolite 3-methoxy-4-hydroxyphenylglycol inhibit lymphocyte chemotaxis: Role of alpha- and beta-adrenoreceptors

The capacity of noradrenaline (NA) and its end metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) to modulate the chemotaxis of lymphocytes from a primary immunocompetent organ (thymus) and a secondary one (spleen) was investigated over a range of concentrations from 10^–12 M to 10^–5 M. Lymphocyte chemotaxis was evaluated in a Boyden chamber. The results indicated that 10^–5 M of NA inhibits the chemotaxis of lymphocytes from both the immunocompetent organs studied, and that this effect is blocked by either propranolol (10^–6 M) or phentolamine (10^–5 M). Similarly, 10^–5 M of MHPG induced a decrease in the chemotaxis capacity of the lymphocytes. In conclusion, high physiological concentrations of NA and its end metabolite modulate the mobility of lymphocytes, and the participation of both alpha and beta adrenoreceptors is necessary, showing a new aspect of neuroimmune interactions.     

Regulation of phagocytic process of macrophages by noradrenaline and its end metabolite 4-hydroxy-3-metoxyphenyl-glycol. Role of α- and β- adrenoreceptors

The regulatory capacity of noradrenaline and its end metabolite 4-hydroxy-3-metoxyphenylglycol (HMPG) on the complete phagocytic process of macrophages were investigated. Either noradrenaline or HMPG did not modify adherence. However, 10^–12 M of noradrenaline stimulated the chemotaxis of macrophages, mainly mediated by -adrenergic receptors. In contrast, 10^–12 M of HMPG induced an opposed effect on this stage of the phagocytic process. To stimulate phagocytosis, it is necessary to employ a higher concentration (10^–5 M) of noradrenaline and this effect was blocked with either 10^–6 M propranolol or 10^–6 M phentolamine, and maintained by HMPG. Noradrenaline and HMPG did not modify the microbicide capacity of macrophages (measured by O₂ ^– production after phagocytosis). In conclusion, noradrenaline modulates the phagocytic process of macrophages, and this modulation is completed by HMPG, maintaining the phagocytic functions at physiologically optimal levels. Modulation of chemotaxis is mainly mediated by a-receptors and phagocytosis needs both - and -receptor-stimulation.     

Tracing the origin of the RACTK1 K(+) channel

Potassium secretion by the kidney is vital for the maintenance of K(+) homeostasis. RACTK1, a putative inwardly rectifying potassium channel cloned from cultured rabbit collecting duct cells, has been proposed to play a role in this process. However, the lack of homology with any other cloned potassium channel and the inability to reproduce the results across different laboratories has brought into question the existence of RACTK1. Recently, it has been suggested that RACTK1 is a contamination from Escherichia coli. In this work we add conclusive evidence supporting the bacterial origin of RACTK1. Using both genomic PCR and RT-PCR we were unable to detect RACTK1 in a number of mammalian species. In addition sequencing of RACTK1 cDNA confirmed a complete homology between RACTK1 and a region of E. coli genomic DNA. Finally, a hypothesis on how RACTK1 could have been generated from a contamination by E. coli genomic DNA is presented.     

Modulation of Adherence and Chemotaxis of Macrophages by Norepinephrine. Influence of Ageing

We evaluated thein vitro effect of norepinephrine (NE), over the range of concentrations between 10^-12 M and 10^-3 M, on adherence (to plastic surfaces) and chemotaxis (in a Boyden chamber) of peritoneal macrophages from BALB/c mice of different ages: young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks). Increased adherence was induced by 10^-12 M of NE in macrophages from young, adult, mature and old mice. Also, 10^-9 M stimulated adherence in old animals, 10^-5 M in mature mice, and 10^-3 M in both young and old mices. With respect to chemotaxis, the low concentration of NE (10^-12 M) was stimulatory only in young and adult animals, higher concentrations (10^-5 M and 10^-7 M) were inhibitory for macrophages from mature and old animals, and the highest concentration of NE (10^-3M) stimulated this capacity of macrophages only in young and mature animals. The conclusion is that while the mobility of macrophages to the focus of infection (i.e. chemotaxis) is stimulated by low concentrations of NE (10^-12, M) only in young-adult animals, this neurotransmitter induces a decline in this capacity in mature and old mice at high concentrations (10^-5 M - 10^-7 M). Also, macrophages from old animals have lost the capacity to respond to pharmacological (10^-3 M) concentrations of NE. The lower capacity of response to NE by macrophages from old animals possibly contributes to immunosenescence.     

Isolation and structure elucidation of new cytotoxic steroids from the gorgonian Leptogorgia sarmentosa

The gorgonian Leptogorgia sarmentosa contains three new steroids, (20S)-20-hydroxycholestane-3,16-dione (1), (16S, 20S)-16,20-dihydroxycholestan-3-one (2), and (20S)-20-hydroxycholest-1-ene-3,16-dione (3) together with a known related compound (4). Their structures were defined by spectroscopic analysis. The new steroids exhibited significant cytotoxicity against four tumor cell lines (ED50 = 1 microg/ml).     

Detection of Cyclospora cayetanensis in Wastewater

Cyclospora cayetanensis causes diarrheal disease worldwide without a confirmed mode of transmission. Wastewater was examined for the presence of this organism. Oocysts were detected microscopically, and their identity was confirmed by molecular techniques. These findings verify that current techniques can isolate Cyclospora oocysts and suggest that fecally contaminated water may act as a vehicle of transmission.     

Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium

Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady‐state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral‐buffered formalin and paraffin‐embedded. Nestin expression was examined by an immunohistochemical peroxidase‐based method. Nestin‐positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin‐positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin‐positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow‐derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases.     

Serum Resistin and Glomerular Filtration Rate in Patients with Type 2 Diabetes

BackgroundHigh serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss.MethodsThe cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US).ResultsSerum resistin was inversely associated with eGFR in SGR [β (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73m², p = 0.019] and in Boston [β (SE) = -5.31 (0.74) ml/min/1.73m², p < 0.001] samples, as well as in the two studies combined [β (SE) = -3.42 (0.52) ml/min/1.73m², p < 0.001]. The association was unaffected by adjustment for smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy: β (SE) for one SD of resistin increment = -1.07 (0.70), p = 0.02; -5.50 (0.88), p < 0.001; and -2.81 (0.55) ml/min/1.73m², p < .001, in SGR, Boston and the two studies combined, respectively. The association was significantly stronger in men than in women (p for resistin-by-gender interaction = 0.003). For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.73m² increased by 22% (OR = 1.22; 95% CI 1.02–1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38–2.07; p < 0.001) in Boston sample, and 47% (OR = 1.47; 95% CI 1.29–1.68; p < 0.001) in the two studies considered together. Similar associations were observed in the adjusted model: OR 95% CI for each SD resistin increment being 1.23 (1.03–1.46), p = 0.021; 1.52 (1.20–1.92), p < 0.001; 1.33 (1.16–1.53), p < 0.001, in SGR, Boston and the two studies combined, respectively.ConclusionsThis is the first report of an association between high serum resistin and low eGFR in patients with T2D of European ancestry.     

Ageostrophic Frontal Processes Controlling Phytoplankton Production in the Catalano-Balearic Sea (Western Mediterranean)

Buoyancy-induced unstable boundary currents and the accompanying retrograde density fronts are often the sites of pronounced mesoscale activity, ageostrophic frontal processes, and associated high biological production in marginal seas. Biophysical model simulations of the Catalano-Balearic Sea (Western Mediterranean) illustrated that the unstable and nonlinear southward frontal boundary current along the Spanish coast resulted in a strain-driven frontogenesis mechanism. High upwelling velocities of up to 80 m d^-1 injected nutrients into the photic layer and promoted enhanced production on the less dense, onshore side of the front characterized by negative relative vorticity. Additional down-front wind stress and heat flux (cooling) intensified boundary current instabilities and thus ageostrophic cross-frontal circulation and augmented production. Specifically, entrainment of nutrients by relatively strong buoyancy-induced vertical mixing gave rise to a more widespread phytoplankton biomass distribution within the onshore side of the front. Mesoscale cyclonic eddies contributed to production through an eddy pumping mechanism, but it was less effective and more limited regionally than the frontal processes. The model was configured for the Catalano-Balearic Sea, but the mechanisms and model findings apply to other marginal seas with similar unstable frontal boundary current systems.