Alveolar macrophages release an insulin-like growth factor I-type molecule.
Publication Type | Academic Article |
Authors | Rom W, Basset P, Fells G, Nukiwa T, Trapnell B, Crysal R |
Journal | J Clin Invest |
Volume | 82 |
Issue | 5 |
Pagination | 1685-93 |
Date Published | 11/01/1988 |
ISSN | 0021-9738 |
Keywords | Insulin-Like Growth Factor I, Macrophages, Pulmonary Alveoli, Somatomedins |
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 a 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. |
DOI | 10.1172/JCI113781 |
PubMed ID | 3183063 |
PubMed Central ID | PMC442738 |