Morphometric analysis of insulin-like growth factor-I localization in lung tissues of patients with idiopathic pulmonary fibrosis

被引:67
作者
Uh, ST
Inoue, Y
King, TE
Chan, ED
Newman, LS
Riches, DWH
机构
[1] Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA
[2] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO USA
[5] Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO USA
[6] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA
关键词
D O I
10.1164/ajrccm.158.5.9804025
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Insulin-like growth factor-1 (IGF-1) has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through its ability to stimulate fibroblast proliferation and collagen synthesis. However, although alveolar macrophages (AM) have been shown to express this growth factor, it is likely to also have other cellular sources. We sought to determine the distribution of cells expressing IGF-1 in lung tissues obtained from 10 patients with IPF and 10 control subjects. We evaluated the levels of IGF-1 and of a macrophage/monocyte-specific marker, CD68, by immunocytochemistry and quantified by morphometry. In control subjects, IGF-1 was localized principally to AM. In contrast, in IPF patients IGF-0 was localized to AM, interstitial macrophages, alveolar epithelial cells, and ciliated columnar epithelial cells. The normalized volume density (Vv) of IGF-1-positive (IGF-1(+)) interstitial macrophages (Vv of IGF-1(+) interstitial macrophages/Vv of lung x 100) was increased in patients with IPF as compared with control subjects, and the ratio of Vv of IGF-1(+) to CD68(+) interstitial macrophages correlated with: (1) the degree of clinical impairment in patients with IPF as measured by their clinical-radiologic-physiologic (CRP) score; and (2) the degree of collagen deposition in the interstitium. These findings support a role for interstitial macrophages as a source of IGF-1 in IPF.
引用
收藏
页码:1626 / 1635
页数:10
相关论文
共 41 条
[2]  
ADAMSON IYR, 1991, LAB INVEST, V64, P339
[3]   PLATELET-DERIVED GROWTH-FACTOR IN IDIOPATHIC PULMONARY FIBROSIS [J].
ANTONIADES, HN ;
BRAVO, MA ;
AVILA, RE ;
GALANOPOULOS, T ;
NEVILLEGOLDEN, J ;
MAXWELL, M ;
SELMAN, M .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (04) :1055-1064
[4]   ENHANCED INSULIN-LIKE GROWTH-FACTOR MOLECULES IN IDIOPATHIC PULMONARY FIBROSIS [J].
ASTON, C ;
JAGIRDAR, J ;
LEE, TC ;
HUR, T ;
HINTZ, RL ;
ROM, WN .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1995, 151 (05) :1597-1603
[5]   MECHANISMS OF PULMONARY FIBROSIS - SPONTANEOUS RELEASE OF THE ALVEOLAR MACROPHAGE-DERIVED GROWTH-FACTOR IN THE INTERSTITIAL LUNG DISORDERS [J].
BITTERMAN, PB ;
ADELBERG, S ;
CRYSTAL, RG .
JOURNAL OF CLINICAL INVESTIGATION, 1983, 72 (05) :1801-1813
[6]   SILICA-INDUCED PULMONARY FIBROSIS INVOLVES THE REACTION OF PARTICLES WITH INTERSTITIAL RATHER THAN ALVEOLAR MACROPHAGES [J].
BOWDEN, DH ;
HEDGECOCK, C ;
ADAMSON, IYR .
JOURNAL OF PATHOLOGY, 1989, 158 (01) :73-80
[7]   INFLUENCE OF AGE AND LONG-TERM DIETARY RESTRICTION ON PLASMA INSULIN-LIKE GROWTH FACTOR-I (IGF-1), IGF-1 GENE-EXPRESSION, AND IGF-1 BINDING-PROTEINS [J].
BREESE, CR ;
INGRAM, RL ;
SONNTAG, WE .
JOURNALS OF GERONTOLOGY, 1991, 46 (05) :B180-B187
[8]   INTERSTITIAL PULMONARY MACROPHAGES PRODUCE PLATELET-DERIVED GROWTH-FACTOR THAT STIMULATES RAT LUNG FIBROBLAST PROLIFERATION INVITRO [J].
BRODY, AR ;
BONNER, JC ;
OVERBY, LH ;
BADGETT, A ;
KALTER, V ;
KUMAR, RK ;
BENNETT, RA .
JOURNAL OF LEUKOCYTE BIOLOGY, 1992, 51 (06) :640-648
[9]   INSULIN-LIKE GROWTH-FACTOR-I IS A MAJOR FIBROBLAST MITOGEN PRODUCED BY PRIMARY CULTURES OF HUMAN AIRWAY EPITHELIAL-CELLS [J].
CAMBREY, AD ;
KWON, OJ ;
GRAY, AJ ;
HARRISON, NK ;
YACOUB, M ;
BARNES, PJ ;
LAURENT, GJ ;
CHUNG, KF .
CLINICAL SCIENCE, 1995, 89 (06) :611-617
[10]  
CHAN ED, 1998, INTERSTITIAL LUNG DI, P135