Activated alveolar macrophages express the insulin-like growth factor-I receptor

Our plain-English summary of Activated alveolar macrophages express the insulin-like growth factor-I receptor, by W.N. Rom, P. Pääkkö (American Journal of Respiratory Cell and Molecular Biology, 1991).

The study

• Authors: W.N. Rom, P. Pääkkö
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1991;4(5):432-9
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Alveolar macrophages (AM) recovered from the lower respiratory tract of individuals with interstitial lung disease (ILD) proliferate at a 2- to 15-fold increased rate (P.B. Bitterman et al. 1984. J. Clin. Invest. 74:460-469). Normal AM stimulated with immune complexes or asbestos release platelet-derived growth factor and insulin-like growth factor-I (IGF-I), and AM activated in vivo in ILD release these growth factors. We evaluated normal unstimulated and activated AM for the receptor for IGF-I to determine if macrophage IGF-I could be involved in the enhanced macrophage proliferation. Although normal AM did not have specific 125I-labeled recombinant IGF-I binding, AM activated by chrysotile asbestos or lipopolysaccharide in vitro or from individuals with ILD had detectable binding that could be inhibited by an anti-IGF-I receptor monoclonal antibody in a dose-dependent fashion. Autoradiography with 125I-labeled recombinant IGF-I revealed binding to the IGF-I receptor on the surface of activated AM, and the percentage of labeled cells was reduced with anti-IGF-I receptor monoclonal antibody or excess unlabeled recombinant IGF-I. Hybridization of total AM RNA to a 32P-labeled IGF-I receptor riboprobe using solution hybridization demonstrated IGF-I receptor mRNA transcripts in AM from an individual with asbestosis, consistent with active expression of the IGF-I receptor gene. In the context of the known role of IGF-I as a growth factor for many cells, these data are consistent with the concept that IGF-I and its receptor may play an important role in the proliferation of AM in the inflamed lower respiratory tract.

In plain English

This laboratory study tested whether alveolar macrophages carry the receptor for insulin-like growth factor-I (IGF-I), a growth signal. Alveolar macrophages are immune cells, here washed out of the lungs by bronchoalveolar lavage. Cells came from 10 men with asbestos exposure, 4 people with idiopathic pulmonary fibrosis and 4 normal volunteers without asbestos exposure. Macrophages from normal volunteers showed no detectable receptor binding. After 24 hours in the laboratory with chrysotile asbestos or lipopolysaccharide, their binding increased markedly. In the 14 people with interstitial lung disease, macrophages averaged 56,914 receptors per cell. None of the 4 normal subjects showed specific binding. On slides, 4 to 14% of macrophages from 5 people with lung disease were labeled, compared with under 1% from normal individuals. Receptor gene messages were found in macrophages from one person with asbestosis, with only a faint signal from a normal volunteer. The authors noted that blocking agents never reduced binding to zero. They concluded that the data are consistent with IGF-I and its receptor possibly playing an important role in macrophage multiplication in the inflamed lung.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study of human alveolar macrophages, using receptor-binding assays, autoradiography and RNA hybridization
• Who was studied: Alveolar macrophages obtained by bronchoalveolar lavage from 10 male nonsmokers or ex-smokers with asbestos exposure, 4 ex-smoker patients with idiopathic pulmonary fibrosis (IPF), and 4 normal control subjects with no asbestos exposure; New York University / Bellevue Hospital
• Exposure: Normal macrophages were stimulated in the laboratory with chrysotile asbestos (100 micrograms per ml) or lipopolysaccharide (10 micrograms per ml) for 24 hours. Macrophages from people with asbestos exposure or IPF were tested without further stimulation.
• Main results:
  • In unstimulated macrophages from normal individuals, no specific IGF-I receptor binding was detected.
  • After normal macrophages were stimulated with chrysotile asbestos or lipopolysaccharide for 24 hours, specific binding increased markedly.
  • In macrophages from one individual with asbestosis, the number of receptors was 11.9 x 10 to the 4th per cell, with a dissociation constant of 21.7 x 10 to the minus 9 M.
  • Across the 14 individuals with interstitial lung disease, the mean was 56,914 IGF-I receptors per cell (spread printed as plus or minus 15).
  • None of the four normal subjects had total binding greater than nonspecific binding.
  • On autoradiography, macrophages from normal individuals had no or few (under 1%) labeled cells, while those from individuals with interstitial lung disease (n = 5) had 4 to 14% of cells labeled.
  • An anti-IGF-I receptor monoclonal antibody substantially reduced specific binding (macrophages tested from seven individuals with interstitial lung disease). An irrelevant control antibody had no effect.
  • Macrophages from one individual with asbestosis expressed a 336-nucleotide IGF-I receptor transcript, while macrophages from a normal individual gave only a faint signal.
• The authors' conclusion: The authors concluded that the data are consistent with the concept that IGF-I and its receptor may play an important role in the proliferation of alveolar macrophages in the inflamed lower respiratory tract.
• Limitations the authors state:
  • Neither the anti-receptor antibody nor excess unlabeled IGF-I reduced binding to zero. The authors said this suggests an alternative explanation, such as an IGF-I binding protein on the surface of activated cells.
  • The amounts of receptor mRNA were in the picogram range, too low for Northern analysis.
  • Macrophages from people with chronic inflammatory lung disease already proliferate and release IGF-I on their own, which made IGF-I-induced proliferation difficult to evaluate.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Interstitial Lung Disease, Platelet-Derived Growth Factor (PDGF), Macrophage, Chrysotile, Monoclonal Antibody.

Related studies

• Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor — W.N. Rom (1991)
• Secretion of fibronectin by mineral dust-derived alveolar macrophages and activated peritoneal macrophages — R. Davies, G. Erdogdu (1989)
• Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages — P.W. Noble, F.R. Lake, et al. (1993)
• Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model — T.C. Lee, L.I. Gold, et al. (1997)
• Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia — E.H. Strøm, F. Skjørten, et al. (1991)
• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)

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