Effect of endothelin-1 on α-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases

被引:61
作者
Shahar, I [1 ]
Fireman, E
Topilsky, M
Grief, J
Schwarz, Y
Kivity, S
Ben-Efraim, S
Spirer, Z
机构
[1] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Pulm Dis, IL-69978 Tel Aviv, Israel
[2] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Allergy Ctr, IL-69978 Tel Aviv, Israel
[3] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Internal Med E, IL-69978 Tel Aviv, Israel
[4] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
[5] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dana Childrens Hosp, IL-69978 Tel Aviv, Israel
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1999年 / 21卷 / 11期
关键词
ET-1; fibroblasts; alpha-smooth muscle actin; interstitial lung diseases;
D O I
10.1016/S0192-0561(99)00056-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Endothelin-l (ET-I) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AIM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to alpha-smooth muscle actin (alpha-SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects, The expression of alpha-SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for alpha-SM actin in all SA acid control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for alpha-SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of alpha-SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease H-3-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating alpha-SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD. (C) 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:759 / 775
页数:17
相关论文
共 35 条
[1]  
ADLER KB, 1989, LAB INVEST, V60, P473
[2]   DEPENDENCE OF COLLAGEN REMODELING ON ALPHA-SMOOTH MUSCLE ACTIN EXPRESSION BY FIBROBLASTS [J].
ARORA, PD ;
MCCULLOCH, CAG .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 159 (01) :161-175
[3]   ENDOTHELINS AND PULMONARY-DISEASES [J].
BARNES, PJ .
JOURNAL OF APPLIED PHYSIOLOGY, 1994, 77 (03) :1051-1059
[4]   GROWTH REGULATORY PROPERTIES OF ENDOTHELINS [J].
BATTISTINI, B ;
CHAILLER, P ;
DORLEANSJUSTE, P ;
BRIERE, N ;
SIROIS, P .
PEPTIDES, 1993, 14 (02) :385-399
[5]   INCREASED LEVELS OF ENDOTHELIN-1 IN BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH SYSTEMIC-SCLEROSIS CONTRIBUTE TO FIBROBLAST MITOGENIC ACTIVITY IN-VITRO [J].
CAMBREY, AD ;
HARRISON, NK ;
DAWES, KE ;
SOUTHCOTT, AM ;
BLACK, CM ;
DUBOIS, RM ;
LAURENT, GJ ;
MCANULTY, RJ .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 11 (04) :439-445
[6]  
DARBY I, 1990, LAB INVEST, V63, P21
[7]   TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCES ALPHA-SMOOTH MUSCLE ACTIN EXPRESSION IN GRANULATION-TISSUE MYOFIBROBLASTS AND IN QUIESCENT AND GROWING CULTURED FIBROBLASTS [J].
DESMOULIERE, A ;
GEINOZ, A ;
GABBIANI, F ;
GABBIANI, G .
JOURNAL OF CELL BIOLOGY, 1993, 122 (01) :103-111
[8]  
DESMOULIERE A, 1992, LAB INVEST, V67, P716
[9]  
Dubin D, 1989, J VASC MED BIOL, V1, P150
[10]   ENDOTHELINS, PEPTIDES WITH POTENT VASOACTIVE PROPERTIES, ARE PRODUCED BY HUMAN MACROPHAGES [J].
EHRENREICH, H ;
ANDERSON, RW ;
FOX, CH ;
RIECKMANN, P ;
HOFFMAN, GS ;
TRAVIS, WD ;
COLIGAN, JE ;
KEHRL, JH ;
FAUCI, AS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (06) :1741-1748