Am. J. Respir. Crit. Care Med., Volume 158, Number 5, November 1998, 1626-1635

Morphometric Analysis of Insulin-like Growth Factor-I Localization in Lung Tissues of Patients with Idiopathic Pulmonary Fibrosis

SOO-TAEK UH, YOSHIKAZU INOUE, TALMADGE E. KING Jr., EDWARD D. CHAN, LEE S. NEWMAN, and DAVID W. H. RICHES

Departments of Pediatrics and Medicine, National Jewish Medical and Research Center; and Departments of Biochemistry and Molecular Genetics, Pharmacology, and Immunology, and Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado

Insulin-like growth factor-I (IGF-I) 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-I in lung tissues obtained from 10 patients with IPF and 10 control subjects. We evaluated the levels of IGF-I and of a macrophage/monocyte-specific marker, CD68, by immunocytochemistry and quantified by morphometry. In control subjects, IGF-I was localized principally to AM. In contrast, in IPF patients IGF-I was localized to AM, interstitial macrophages, alveolar epithelial cells, and ciliated columnar epithelial cells. The normalized volume density (Vv) of IGF-I-positive (IGF-I⁺) interstitial macrophages (Vv of IGF-I⁺ interstitial macrophages/Vv of lung × 100) was increased in patients with IPF as compared with control subjects, and the ratio of Vv of IGF-I⁺ 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-I in IPF.

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