CALU-3 - A HUMAN AIRWAY EPITHELIAL-CELL LINE THAT SHOWS CAMP-DEPENDENT CL- SECRETION

被引:316
作者
SHEN, RQ
FINKBEINER, WE
WINE, JJ
MRSNY, RJ
WIDDICOMBE, JH
机构
[1] UNIV CALIF SAN FRANCISCO,CYST FIBROSIS RES CTR,INST CARDIOVASC RES,DEPT PHYSIOL,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,CYST FIBROSIS RES CTR,CARDIOVASC RES INST,DEPT PATHOL,SAN FRANCISCO,CA 94143
[3] STANFORD UNIV,DEPT PSYCHOL,STANFORD,CA 94305
[4] GENENTECH INC,S SAN FRANCISCO,CA 96080
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1994年 / 266卷 / 05期
关键词
CELL CULTURE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR;
D O I
10.1152/ajplung.1994.266.5.L493
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Of 12 cell lines derived from human lung cancers, only Calu-3 cells showed high transepithelial resistance (R(te)) and increases in short-circuit current (I-sc) in response to mediators. Calu-3 cells formed polarized monolayers with tight junctions and R(te) of similar to 100 Omega.cm(2). Baseline I-sc was similar to 35 mu A/cm(2) and was increased by similar to 75 mu A/cm(2) on elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by isoproterenol. Flux studies showed that the increase in I-sc was due to Cl- secretion. Forskolin and permeant analogues of cAMP also increased I-sc. Consistent with the presence of cAMP-dependent Cl- secretion, immunoprecipitation demonstrated the presence of the cystic fibrosis transmembrane conductance regulator (CFTR). Bradykinin, methacholine, trypsin, and histamine all transiently (15-30 s) elevated I-sc, probably by increasing intracellular Ca concentration. Experiments in which the basolateral membrane was permeabilized with nystatin indicated that CFTR was substantially activated under baseline conditions and that Ca-activated Cl- channels were absent from the apical membrane. We anticipate that Calu-3 cells will prove useful in the study of Cl- secretion and other functions of human airway epithelial cells.
引用
收藏
页码:L493 / L501
页数:9
相关论文
共 39 条
[1]   CALCIUM AND CAMP ACTIVATE DIFFERENT CHLORIDE CHANNELS IN THE APICAL MEMBRANE OF NORMAL AND CYSTIC-FIBROSIS EPITHELIA [J].
ANDERSON, MP ;
WELSH, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6003-6007
[2]  
BASBAUM CB, 1990, ANNU REV PHYSIOL, V52, P97
[3]   NA+ TRANSPORT IN CYSTIC-FIBROSIS RESPIRATORY EPITHELIA - ABNORMAL BASAL RATE AND RESPONSE TO ADENYLATE-CYCLASE ACTIVATION [J].
BOUCHER, RC ;
STUTTS, MJ ;
KNOWLES, MR ;
CANTLEY, L ;
GATZY, JT .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (05) :1245-1252
[4]  
BUCHANAN JA, 1990, J CELL SCI, V95, P109
[5]   PROPAGATION OF DIFFERENTIATING NORMAL HUMAN TRACHEOBRONCHIAL EPITHELIAL-CELLS IN SERUM-FREE MEDIUM [J].
CHOPRA, DP ;
SULLIVAN, J ;
WILLE, JJ ;
SIDDIQUI, KM .
JOURNAL OF CELLULAR PHYSIOLOGY, 1987, 130 (02) :173-181
[6]   CHARACTERIZATION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IN A COLONOCYTE CELL-LINE [J].
COHN, JA ;
NAIRN, AC ;
MARINO, CR ;
MELHUS, O ;
KOLE, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (06) :2340-2344
[7]   ELECTRICAL-PROPERTIES OF DOG TRACHEAL EPITHELIAL-CELLS GROWN IN MONOLAYER-CULTURE [J].
COLEMAN, DL ;
TUET, IK ;
WIDDICOMBE, JH .
AMERICAN JOURNAL OF PHYSIOLOGY, 1984, 246 (03) :C355-C359
[8]   CFTR EXPRESSION AND CHLORIDE SECRETION IN POLARIZED IMMORTAL HUMAN BRONCHIAL EPITHELIAL-CELLS [J].
COZENS, AL ;
YEZZI, MJ ;
KUNZELMANN, K ;
OHRUI, T ;
CHIN, L ;
ENG, K ;
FINKBEINER, WE ;
WIDDICOMBE, JH ;
GRUENERT, DC .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 10 (01) :38-47
[9]  
COZENS AL, 1991, ADV EXP MED BIOL, V290, P187
[10]   CHARACTERIZATION OF IMMORTAL CYSTIC-FIBROSIS TRACHEOBRONCHIAL GLAND EPITHELIAL-CELLS [J].
COZENS, AL ;
YEZZI, MJ ;
CHIN, L ;
SIMON, EM ;
FINKBEINER, WE ;
WAGNER, JA ;
GRUENERT, DC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (11) :5171-5175