IL-4 increases surfactant and regulates metabolism in vivo

被引:54
作者
Ikegami, M [1 ]
Whitsett, JA [1 ]
Chroneos, ZC [1 ]
Ross, GF [1 ]
Reed, JA [1 ]
Bachurski, CJ [1 ]
Jobe, AH [1 ]
机构
[1] Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA
关键词
transgenic mice; saturated phosphatidylcholine; surfactant protein A; surfactant protein D; alveolar proteinosis;
D O I
10.1152/ajplung.2000.278.1.L75
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
IL-4 increases surfactant and regulates metabolism in vivo. Am. J. Physiol. Lung Cell. Mel. Physiol. 278: L75-L80, 2000.-Mice that express interleukin (IL)-4 in Clara cells (CCSP-IL-4) develop chronic airway inflammation and an alveolar proteinosis-like syndrome. To identify the role of IL-4 in surfactant homeostasis, we measured lipid and protein metabolism in the lungs of CCSP-IL-4 mice in vivo. Alveolar saturated phosphatidylcholine (Sat PC) pools were increased 6.5-fold and lung tissue Sat PC pools were increased 4.8-fold in the IL-4 transgenic mice. Whereas surfactant protein (SP) A was increased proportionately to Sat PC, SP-D was increased approximately 90-fold in the IL-4 mice compared with wild-type mice and was associated with 2.8-fold increase in SP-D mRNA. The incorporation of palmitate and choline into Sat PC was increased about twofold in CCSP-IL-4 mice. Although trace doses of radiolabeled Sat PC were cleared from the air spaces and lungs of CCSP-IL-4 mice more slowly than in wild-type mice, net clearance of Sat PC from the lungs of CCSP-IL-4 mice was sixfold higher in the IL-4 mice than in wild-type mice because of the larger Sat PC pool sizes. Expression of IL-4 in Clara cells increased surfactant lipid synthesis and clearance, establishing a new equilibrium with increased surfactant pools and an alveolar proteinosis associated with a selective increase in SP-D protein, demonstrating a previously unexpected effect of IL-4 in pulmonary surfactant homeostasis.
引用
收藏
页码:L75 / L80
页数:6
相关论文
共 31 条
[1]  
BARTLETT GR, 1959, J BIOL CHEM, V234, P466
[2]   Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D [J].
Botas, C ;
Poulain, F ;
Akiyama, J ;
Brown, C ;
Allen, L ;
Goerke, J ;
Clements, J ;
Carlson, E ;
Gillespie, AM ;
Epstein, C ;
Hawgood, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11869-11874
[3]   MECHANISMS OF PERSISTENT AIRWAY INFLAMMATION IN ASTHMA - A ROLE FOR T-CELLS AND T-CELL PRODUCTS [J].
BUSSE, WW ;
COFFMAN, RL ;
GELFAND, EW ;
KAY, AB ;
ROSENWASSER, LJ .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1995, 152 (01) :388-393
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]   Collectins and pulmonary host defense [J].
Crouch, EC .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1998, 19 (02) :177-201
[6]   THE RELATIONSHIP BETWEEN INTRACELLULAR AND EXTRACELLULAR SURFACTANT PHOSPHOLIPIDS IN THE LUNGS OF RABBITS AND THE EFFECTS OF SILICA-INDUCED LUNG INJURY [J].
DETHLOFF, LA ;
GILMORE, LB ;
HOOK, GER .
BIOCHEMICAL JOURNAL, 1986, 239 (01) :59-67
[7]   Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression [J].
Dirksen, U ;
Nishinakamura, R ;
Groneck, P ;
Hattenhorst, U ;
Nogee, L ;
Murray, R ;
Burdach, S .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (09) :2211-2217
[8]   RECYCLING OF SURFACTANT IN BLACK AND BEIGE MICE - POOL SIZES AND KINETICS [J].
GROSS, NJ ;
BARNES, E ;
NARINE, KR .
JOURNAL OF APPLIED PHYSIOLOGY, 1988, 64 (05) :2017-2025
[9]   EFFECTS OF A SURFACTANT-ASSOCIATED PROTEIN AND CALCIUM-IONS ON THE STRUCTURE AND SURFACE-ACTIVITY OF LUNG SURFACTANT LIPIDS [J].
HAWGOOD, S ;
BENSON, BJ ;
HAMILTON, RL .
BIOCHEMISTRY, 1985, 24 (01) :184-190
[10]   Lung epithelium-specific proteins - Characteristics and potential applications as markers [J].
Hermans, C ;
Bernard, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1999, 159 (02) :646-678