Basal secretion of lysozyme from human airways in vitro.

The aim of this study was to examine the basal release of lysozyme from isolated human lung tissues. Measurements of lysozyme in the fluids derived from lung preparations were performed using a rate-of-lysis assay subsequent to acidification of the biological samples. Lysozyme released from bronchial preparations into fluids was greater than that observed for parenchymal tissues. The lysozyme quantities detected in bronchial fluids were not modified by removal of the surface epithelium. Furthermore, the quantities of lysozyme in bronchial fluids was correlated with the size of the bronchial preparations. These results suggest that the lysozyme was principally secreted by the human bronchi (submucosal layer) rather than by parenchyma tissues and that a greater release was observed in the proximal airways

MUC5AC mucin release from human airways in vitro: effects of indomethacin and Bay X1005.

BACKGROUND: Increased secretion of mucus is a hallmark of many respiratory diseases and contributes significantly to the airflow limitation experienced by many patients. While the current pharmacological approach to reducing mucus and sputum production in patients is limited, clinical studies have suggested that drugs which inhibit the cyclooxygenase and/or 5-lipoxygenase enzymatic pathways may reduce secretory activity in patients with airway disease. AIM: This study was performed to investigate the effects of indomethacin (cyclooxygenase inhibitor) and Bay x 1005 (5-lipoxygenase inhibitor) on MUC5AC release from human airways in vitro. METHODS: An immunoradiometric assay was used to determine the quantities of MUC5AC present in the biological fluids derived from human airways in vitro. The measurements were made with a mixture of eight monoclonal antibodies (MAbs; PM8) of which the 21 M1 MAb recognized a recombinant M1 mucin partially encoded by the MUC5AC gene. RESULTS: The quantities of MUC5AC detected in the biological fluids derived from human bronchial preparations were not modified after treatment with indomethacin (cyclooxygenase inhibitor) and/or an inhibitor of the 5-lipoxygenase metabolic pathway (BAY x 1005). CONCLUSION: These results suggest that the cyclooxygenase and 5-lipoxygenase metabolic pathways play little or no role in the release of MUC5AC from human airways

Pulmonary hypertension in infants with congenital heart defects: are leukotrienes involved?

The circulating levels of leukotriene E4 in infants with congenital heart defects, increased pulmonary blood flow and pulmonary arterial hypertension, were determined and compared with infants with decreased pulmonary blood flow (Tetralogy of Fallot). There was no correlation (r=0.38) between the pulmonary arterial pressure (56 ± 4 mmHg) and the leukotriene E4 levels (1.37 ± 0.67 ng/ml blood) measured in peripheral blood samples from the hypertensive group prior to surgery. There was considerable variation in the detectable leukotriene E4 levels in blood samples from different patients. The levels detected in the blood samples between the two groups of patients was similar. These data suggest that neither the surgical repair during cardiopulmonary bypass nor the pulmonary hypertension appeared to modify the leukotriene E4 blood levels in the small number of patients studied

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

ATP induced MUC5AC release from human airways in vitro.

BACKGROUND: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators. AIM: This investigation was performed to determine the release of MUC5AC mucin from human bronchial preparations using the purinergic agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP). METHODS: Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed using individual 1-13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin partially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti-M1 mucin MAbs (PM8), which included both 1-13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological fluids derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma. RESULTS: The anti-M1 monoclonal antibodies labelled epithelial goblet cells. After challenge of human bronchial preparations with ATP, the goblet cells exhibited less staining. In contrast, UTP did not alter the immunolabelling of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP-challenged preparations was increased while UTP had no effect on release. ATP did not alter either the quantities of lysozyme or protein detected in the biological fluids. CONCLUSION: These results suggest that ATP may regulate epithelial goblet cell secretion of MUC5AC mucin from human airways in vitro

Anti-IgE Response in Human Airways: Relative Contribution of Inflammatory Mediators

Heman airway preparations at resting tone were relaxed with either the leukotriene synthesis inhibitor BAY x1005 (3 μM), chlorpheniramine (1 μM) or the thromboxane receptor antagonist BAY u3405 (0.1 μM). The response to anti-IgE (1:1000) was 58 ± 8% of acetylcholine pre-contraction (2.19 ± 0.28 g). Indomethacin (3 μM) enhanced the anti-IgE-induced contraction by 28%. The anti-IgE maximal response was not modified by either chlorpheniramine, BAY x1005 or BAY u3405. When the tissues were treated with either BAY xl005/indomethacin or BAY x1005/chlorpheniramine, the anti-IgE-induced contraction was reduced. In addition, in presence of BAY xl005/indomethacin/chlorpheniramine the response was completely blocked. These results suggest that mediatots released during anti-IgE challenge cause airway contraction which may mask the evaluation of the leukotriene component

Ice–ocean interaction and calving front morphology at two west Greenland tidewater outlet glaciers

Warm, subtropical-originating Atlantic water (AW) has been identified as a primary driver of mass loss across the marine sectors of the Greenland Ice Sheet (GrIS), yet the specific processes by which this water mass interacts with and erodes the calving front of tidewater glaciers is frequently modelled and much speculated upon but remains largely unobserved. We present a suite of fjord salinity, temperature, turbidity versus depth casts along with glacial runoff estimation from Rink and Store glaciers, two major marine outlets draining the western sector of the GrIS during 2009 and 2010. We characterise the main water bodies present and interpret their interaction with their respective calving fronts. We identify two distinct processes of ice–ocean interaction which have distinct spatial and temporal footprints: (1) homogenous free convective melting which occurs across the calving front where AW is in direct contact with the ice mass, and (2) localised upwelling-driven melt by turbulent subglacial runoff mixing with fjord water which occurs at distinct injection points across the calving front. Throughout the study, AW at 2.8 ± 0.2 °C was consistently observed in contact with both glaciers below 450 m depth, yielding homogenous, free convective submarine melting up to ~200 m depth. Above this bottom layer, multiple interactions are identified, primarily controlled by the rate of subglacial fresh-water discharge which results in localised and discrete upwelling plumes. In the record melt year of 2010, the Store Glacier calving face was dominated by these runoff-driven plumes which led to a highly crenulated frontal geometry characterised by large embayments at the subglacial portals separated by headlands which are dominated by calving. Rink Glacier, which is significantly deeper than Store has a larger proportion of its submerged calving face exposed to AW, which results in a uniform, relatively flat overall frontal geometry

The mean circulation of the southwestern Mediterranean Sea: Algerian Gyres

This is a study about the general circulation of the southwestern Mediterranean Sea based on observations of currents carried out in the southwestern Mediterranean Sea in the framework of the Mass Transfer and Ecosystem Response (MATER) program (EEC/MAST3 program). From July 1997 to August 2002, profiling floats (MEDPROF experiment), isobaric floats (LIWEX experiment), and moored current meters (ELISA experiment) give evidence of two large-scale barotropic cyclonic circulations, the here-called Western and Eastern Algerian Gyres, centered around [3730′N, 230′E] and [3830′N, 600′E], respectively. These gyres have typical horizontal scales of 100–300 km and are characterized by orbital velocities of about 5 cm/s corresponding to rotational periods of about 4 months. They are strongly related to the bottom topography of the basin and to the planetary vorticity gradient: closed f/H isocontours (f is the planetary vorticity, H the water depth) correspond to the locations of the gyres and favor such circulations as free geostrophic modes. A linear and barotropic model is used to investigate the possibility of wind driving, but the results suggest that the wind stress is not responsible for establishing such circulations. The boundary currents flowing along the continental slope of Africa, Sardinia, and the Balearic Islands are proposed to be the main drivers of these gyres