Alveolar macrophages release an insulin-like growth factor I-type molecule

W. N. Rom, P. Basset, G. A. Fells, T. Nukiwa, B. C. Trapnell, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

Human alveolar macrophages, when activated, release a progression-type growth factor for fibroblasts that signals 'competent' fibroblasts to replicate. The present study demonstrates that this growth activity is an insulin-like growth factor (I (IGF-I)-type molecule. Partial purification of medium conditioned by activated alveolar macrophages using ion exchange and gel filtration chromatography revealed an IGF-I molecule as detected by an anti-IGF-I polyclonal antibody and that the specific activity of the progression-type growth activity tracked with the amount of IGF-I present. In a serum-free complementation test, the increase in fibroblast proliferation by alveolar macrophage IGF-I was reduced in a dose-response manner with an anti-IGF-I monoclonal antibody. The alveolar macrophage IGF-I displaced 125I-IGF-I from its receptor in binding assay utilizing human lung fibroblasts and it stimulated type I IGF receptors purified from human lung fibroblasts to phosphorylate a tyrosine-containing artificial substrate. In contrast to the 7.6-kD serum IGF-I, gel chromatography revealed that the alveolar macrophage IGF-I had an apparent molecular mass of 26 kD, similar to other tissue IGF-Is. Alveolar macrophages expressed IGF-I mRNA transcripts as detected by solution hybridization using a 32P-labeled riboprobe complementary to exons I-II-III of the IGF-I gene. In the context of the known functions of the family of IGF-I molecules in cell growth, IGF-I released by activated alveolar macrophages may play a role in acute and chronic inflammatory disorders.

Original languageEnglish
Pages (from-to)1685-1693
Number of pages9
JournalJournal of Clinical Investigation
Volume82
Issue number5
DOIs
Publication statusPublished - 1 Jan 1988
Externally publishedYes

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Alveolar Macrophages
Insulin-Like Growth Factor I
Fibroblasts
IGF Type 1 Receptor
Gel Chromatography
Growth
Genetic Complementation Test
Lung
Fibroblast Growth Factors
Ion Exchange
Conditioned Culture Medium
Serum
Tyrosine
Exons
Monoclonal Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Alveolar macrophages release an insulin-like growth factor I-type molecule. / Rom, W. N.; Basset, P.; Fells, G. A.; Nukiwa, T.; Trapnell, B. C.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 82, No. 5, 01.01.1988, p. 1685-1693.

Research output: Contribution to journalArticle

Rom, W. N. ; Basset, P. ; Fells, G. A. ; Nukiwa, T. ; Trapnell, B. C. ; Crystal, Ronald. / Alveolar macrophages release an insulin-like growth factor I-type molecule. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 5. pp. 1685-1693.
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