Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium

Chloride (Cl-) secretion by the airway epithelium regulates, in part, the quantity and composition of the respiratory tract fluid, thereby facilitating mucociliary clearance. The rate of Cl- secretion is controlled by apical membrane Cl- channels. Apical Cl- channels are opened and Cl- secretion is stimulated by a variety of hormones and neurotransmitters that increase intracellular levels of cyclic AMP (cAMP). In cystic fibrosis (CF), a common lethal genetic disease of Caucasians, airway, sweat-gland duct, secretory-coil and possibly other epithelia are anion impermeable. This abnormality may explain several of the clinical manifestations of the disease. The Cl- impermeability in CF-airway epithelia has been localized to the apical cell membrane, where regulation of Cl- channels is abnormal: hormonal secretagogues stimulate cAMP accumulation appropriately but Cl- channels fail to open. Here we report that the purified catalytic subunit of cAMP-dependent protein kinase plus ATP opens Cl- channels in excised, cell-free patches of membrane from normal cells, but fails to open Cl- channels in CF cells. These results indicate that in normal cells, the cAMP-dependent protein kinase phosphorylates the Cl- channel or an associated regulatory protein, causing the channel to open. The failure of CF Cl- channels to open suggests a defect either in the channel or in such an associated regulatory protein.     

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung

Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO(3)(-) transport. Without CFTR, airway epithelial HCO(3)(-) secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.     

Segregation of receptor and ligand regulates activation of epithelial growth factor receptor

Interactions between ligands and receptors are central to communication between cells and tissues. Human airway epithelia constitutively produce both a ligand, the growth factor heregulin, and its receptors--erbB2, erbB3 and erbB4 (refs 1-3). Although heregulin binding initiates cellular proliferation and differentiation, airway epithelia have a low rate of cell division. This raises the question of how ligand-receptor interactions are controlled in epithelia. Here we show that in differentiated human airway epithelia, heregulin-alpha is present exclusively in the apical membrane and the overlying airway surface liquid, physically separated from erbB2-4, which segregate to the basolateral membrane. This physical arrangement creates a ligand-receptor pair poised for activation whenever epithelial integrity is disrupted. Indeed, immediately following a mechanical injury, heregulin-alpha activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity. Likewise, when epithelial cells are not separated into apical and basolateral membranes ('polarized'), or when tight junctions between adjacent cells are opened, heregulin-alpha activates its receptor. This mechanism of ligand-receptor segregation on either side of epithelial tight junctions may be vital for rapid restoration of integrity following injury, and hence critical for survival. This model also suggests a mechanism for abnormal receptor activation in diseases with increased epithelial permeability.     

Utah plant types—historical perspective 1840 to 1981—annotated list, and bibliography

New taxa include: Cryptantha cinerea (Torr.) Cronq. var. arenicola Higgins & Welsh; Physaria chambersii Rollins var. sobolifera Welsh (Cruciferae); Phacelia demissa Gray var. minor N. D. Atwood (Hydrophyllaceae); Iris pariensis Welsh (Iridaceae); Astragalus preussii var. cutleri Barneby and Pediomelum aromaticum (Payson) Welsh var. tuhyi Welsh (Leguminosae); Abronia nana Wats. var. harrisii Welsh (Nyctaginaceae); Camissonia atwoodii Cronq. (Onagraceae); Habenaria zothecina Higgins & Welsh (Orchidaceae); Aqiiilegia formosa Fisch. in DC. var. fosteri Welsh (Ranunculaceae). New nomenclatural combinations include: Rhus aromatica Ait. var. simplicifolia (Greene) Cronq. (Anacardiaceae); Lomatium kingii (Wats.) Cronq., L. kingii var. alpinum (Wats.) Cronq. (Apiaceae); Cryptantha cinerea (Torr.) Cronq. var. laxa (Macbr.) Higgins; Mertensia lanceolata (Pursh) DC. var. nivalis (Wats.) Higgins (Boraginaceae); Opuntia erinacea Engelm. var. aurea (Baxter) Welsh (Cactaceae); Arenaria fendleri Gray var. aculeata (Wats.) Welsh, A. fendleri var. eastwoodiae (Rydb.) Welsh, Lychnis apetala L. var. kingii (Wats.) Welsh, Stellaria longipes Goldie var. monantha (Hulten) Welsh (Caryophyllaceae); Draba densifolia Nutt. ex T. & G. var. apiculata (C. L. Hitchc.) Welsh, D. oligosperma Hook. var. juniperina (Dorn) Welsh, Physaria acutifolia Rydb. var. stylosa (Rollins) Welsh, Thelypodiopsis sagittata (Nutt.) Schulz var. ovalifolia (Rydb.) Welsh (Cruciferae); Lotus plebeius (T. Brandg.) Barneby, Lupinus polyphyllus Lindl. in Edwards var. ammophilus (Greene) Barneby, L polyphyllus var. humicola (A. Nels.) Barneby, L. argenteus Pursh var. fulvomaculatus (Payson) Barneby, L. argenteus var. palmeri (Wats.) Barneby, Pediomelum aromaticum (Payson) Welsh, P. epipsilum (Barneby) Welsh, Psoralidium lanceolatum (Pursh) Rydb. var. stenophyllum (Rydb.) Welsh, and P. lanceolatum var. stenostachys (Rydb.) Welsh (Leguminosae); Mirabilis linearis (Pursh) Hiemerl var. decipiens (Standl.) Welsh (Nyctaginaceae); Camissonia boothii var. condensata (Munz) Cronq., C. boothii var. villosa (Wats.) Cronq., C. clavaeformis (Torr. & Frem.) Raven var. purpurascens (Wats.) Cronq., C. scapoidea (T. & G.) var. utahensis (Raven) Welsh, Oenothera caespitosa var. macroglottis (Rydb.) Cronq., Oe. caespitosa var. navajoensis (Wagner, Stockhouse, & Klein) Cronq., Oe. flava (A. Nels.) Garrett var. acutissima (W. L. Wagner) Welsh, and Oe. primiveris Gray var. bufonis (Jones) Cronq. (Onagraceae); Papaver radicatum Rottb. var. pygmaeum (Rydb.) Welsh (Papaveraceae); Dodecatheon pulchellum (Raf.) Merr. var. zionense (Eastw.) Welsh (Primulaceae); Aquilegia flavescens Wats. var. rubicunda (Tidestr.) Welsh, Delphinium andersonii Gray var. scaposum (Greene) Welsh, D. occidentalis (Wats.) Wats. var. barbeyi (Huth) Welsh, and Ranunculus andersonii Gray var. juniperinus (Jones) Welsh (Ranunculaceae); Purshia mexicana (D. Don) Welsh and P. mexicana var. stansburyi (Torr.) Welsh (Rosaceae); Galium mexicanum H.B.K. var. asperrimum (Gray) Higgins & Welsh (Rubiaceae); Castilleja parvula Rydb. var. revealii (N. Holmgren) N. D. Atwood and C. rhexifolia Rydb. var. sulphurea (Rydb.) N. D. Atwood (Scrophulariaceae).     

New variety of Stephanomeria tenuifolia (Compositae) from Utah

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Utah's rare plants revisited

Presented is a current evaluation of the status and distribution of Utah's rare plant species, including those officially listed as endangered or threatened, those under review for listing, those recommended by the Utah Native Plant Society, and those which recently have been removed from consideration. Taxa are discussed alphabetically. Information on status, distribution, habitat, elevation, and specimens deposited at Brigham Young University are included in the discussion of each species. Maps showing the state distribution of each listed or candidate plant are also provided. New combinations include Dalea flavescens (Wats.) Welsh var. epica (Welsh) Welsh & Chatterley and Schoenerambe suffrutescens (Rollins) Welsh & Chatterley.        

Preliminary index of authors of Utah plant names

Presented herein is an index to approximately 800 authors of vascular plant names of Utah. A standardized abbreviation is presented for each author. These are listed alphabetically. Following each abbreviation is the full name and birth and death dates (where available) of each individual. In some cases the date of publication is given when biographical information is not known.     

A fourth species of Oreoxis (Umbelliferae)

Described as a new species is Oreoxis trotteri Welsh & Goodrich from Utah.