Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor

Our plain-English summary of Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor, by W.N. Rom (American Journal of Respiratory Cell and Molecular Biology, 1991).

The study

• Author: W.N. Rom
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1991;4(6):555-9
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The insulin-like growth factor (IGF)-II/mannose-6-phosphate (M6P) receptor, which targets acid hydrolases to lysosomes, is a multifunctional protein with separate binding sites for IGF-II and M6P. The purpose of this study was to determine if alveolar macrophages (AM) and their precursor cells, blood monocytes, expressed this receptor. AM expressed IGF-II/M6P receptors as detected by [125]IGF-II surface binding that was not reduced by recombinant IGF-I or IGF-I receptor monoclonal antibody (alpha IR3). Surface binding was also detected on blood monocytes and could be upregulated approximately 4-fold by incubation with lipopolysaccharide. There were no differences in surface binding by AM lavaged from individuals with asbestos exposure or from normal volunteers. Using the polymerase chain reaction and reverse transcriptase to reverse-transcribe mRNA from mononuclear phagocytes, specific IGF-II/M6P receptor cDNA was amplified and detected by agarose gel electrophoresis from both AM and blood monocytes. The IGF-II/M6P receptor has an intracellular transport role in many cells cycling from the cell surface to the cytoplasm, or binding to phosphorylated acid hydrolases in the Golgi and transporting them to an acidic prelysosomal site where they dissociate and fuse to the lysosomes and IGF-II/M6P recycles to the trans-Golgi. These functions may be particularly important in asbestosis and other interstitial lung diseases where AM are activated, intracellular lysosomes are a prominent morphologic feature, and acid hydrolases are found in recovered lavage fluid.

In plain English

This single-author laboratory study tested whether human alveolar macrophages (lung immune cells) and blood monocytes, their precursor cells, carry the IGF-II/mannose-6-phosphate receptor. This protein helps deliver acid hydrolase enzymes to lysosomes inside cells. Lung cells were collected by bronchoalveolar lavage from five normal volunteers and eight individuals with asbestos exposure. Six of the eight had pleural abnormalities and irregular opacities on chest X-rays. Lavage from the asbestos-exposed group contained increased numbers of cells. Radiolabeled IGF-II bound to the macrophage surface. Across the eight asbestos-exposed individuals the mean was 21,200 plus or minus 8,222 (standard error) receptors per cell, with a median of 11,467. Binding curves were the same for the asbestos-exposed and the unexposed controls. Fresh blood monocytes had 10,632 receptors per cell, and binding rose about 4-fold after treatment with lipopolysaccharide. PCR detected the receptor's genetic message in both cell types. The author suggested that the receptor's functions may be particularly important in asbestosis and other interstitial lung diseases. The author noted that most of the cells' receptors were not examined, and that the binding tests alone did not prove the binding was only to this receptor.

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 study of human cells: surface receptor binding assays and PCR on alveolar macrophages obtained by bronchoalveolar lavage and on blood monocytes
• Who was studied: Five normal volunteers (lifelong nonsmokers with normal lung function and chest X-rays) and eight individuals with asbestos exposure, all of whom underwent bronchoalveolar lavage; blood monocytes came from normal volunteers. Location: New York University Medical Center / Bellevue Hospital, New York. Dates of study not given.
• Exposure: Asbestos exposure (fiber type, products and jobs not specified). In the laboratory, blood monocytes were also stimulated with lipopolysaccharide.
• Main results:
  • Six of the eight asbestos-exposed individuals had pleural abnormalities and irregular opacities on chest X-rays
  • Lavage fluid from the asbestos-exposed individuals contained increased numbers of cells, which the author described as consistent with an alveolar macrophage alveolitis
  • In one asbestos-exposed individual, the binding dissociation constant was 8.7 x 10 to the minus 9 M, with 5,862 receptors per cell
  • Across the eight asbestos-exposed individuals, the mean (plus or minus standard error) was 21,200 plus or minus 8,222 IGF-II receptors per alveolar macrophage, with a median of 11,467
  • Binding curves were the same for alveolar macrophages from asbestos-exposed individuals and from unexposed controls
  • Specific binding was unchanged by excess recombinant IGF-I or by the anti-IGF-I receptor antibody
  • Fresh blood monocytes had 10,632 receptors per cell
  • Surface receptor expression on blood monocytes rose approximately 4-fold after incubation with lipopolysaccharide
  • PCR amplified a 630-nucleotide IGF-II receptor cDNA from alveolar macrophages, and also from fresh blood monocytes and from monocytes cultured for 7 and 14 days
• The authors' conclusion: The author suggested that the receptor's transport functions may be particularly important in asbestosis and other interstitial lung diseases where alveolar macrophages are activated. This was a suggestion, not something the study tested.
• Limitations the authors state:
  • In most cells the surface receptor is a minor share of the total, so the majority of the cells' receptors were not examined by this approach
  • The lack of blocking by the anti-IGF-I receptor antibody does not prove that the binding was only to the IGF-II receptor
  • Affinity cross-linking studies, which would have been definitive, were impractical because of the small amounts of receptor protein on the limited macrophages available

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Monoclonal Antibody, Asbestos Exposure, Interstitial Lung Disease.

Related studies

• Activated alveolar macrophages express the insulin-like growth factor-I receptor — W.N. Rom, P. Pääkkö (1991)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• A synergistic interaction between Bacillus Calmette-Guérin (BCG) and NADPH oxidase stimulants on the production of reactive oxygen metabolites by human mononuclear phagocytes — P.W. Nyberg, S.A. Nordman, et al. (1994)
• Asbestos induces selective release of lysosomal enzymes from mononuclear phagocytes — P. Davies, A.C. Allison, et al. (1974)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B — Z. Ma, T. Otsuki, et al. (1999)

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