Alveolar macrophages release an insulin-like growth factor I-type molecule. (original) (raw)
- Journal List
- J Clin Invest
- v.82(5); 1988 Nov
- PMC442738
J Clin Invest. 1988 Nov; 82(5): 1685–1693.
Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
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.
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- Adams DO, Hamilton TA. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2:283–318. [PubMed] [Google Scholar]
- Takemura R, Werb Z. Secretory products of macrophages and their physiological functions. Am J Physiol. 1984 Jan;246(1 Pt 1):C1–C9. [PubMed] [Google Scholar]
- Nathan CF, Murray HW, Cohn ZA. The macrophage as an effector cell. N Engl J Med. 1980 Sep 11;303(11):622–626. [PubMed] [Google Scholar]
- Nathan CF. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. [PMC free article] [PubMed] [Google Scholar]
- Leibovich SJ, Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975 Jan;78(1):71–100. [PMC free article] [PubMed] [Google Scholar]
- Leibovich SJ, Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol. 1976 Sep;84(3):501–514. [PMC free article] [PubMed] [Google Scholar]
- Bitterman PB, Wewers MD, Rennard SI, Adelberg S, Crystal RG. Modulation of alveolar macrophage-driven fibroblast proliferation by alternative macrophage mediators. J Clin Invest. 1986 Mar;77(3):700–708. [PMC free article] [PubMed] [Google Scholar]
- Hunninghake GW, Gadek JE, Kawanami O, Ferrans VJ, Crystal RG. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol. 1979 Oct;97(1):149–206. [PMC free article] [PubMed] [Google Scholar]
- Crystal RG, Bitterman PB, Rennard SI, Hance AJ, Keogh BA. Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts). N Engl J Med. 1984 Jan 19;310(3):154–166. [PubMed] [Google Scholar]
- Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. [PubMed] [Google Scholar]
- Martinet Y, Bitterman PB, Mornex JF, Grotendorst GR, Martin GR, Crystal RG. Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature. 1986 Jan 9;319(6049):158–160. [PubMed] [Google Scholar]
- Mornex JF, Martinet Y, Yamauchi K, Bitterman PB, Grotendorst GR, Chytil-Weir A, Martin GR, Crystal RG. Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages. J Clin Invest. 1986 Jul;78(1):61–66. [PMC free article] [PubMed] [Google Scholar]
- Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. [PubMed] [Google Scholar]
- Rennard SI, Hunninghake GW, Bitterman PB, Crystal RG. Production of fibronectin by the human alveolar macrophage: mechanism for the recruitment of fibroblasts to sites of tissue injury in interstitial lung diseases. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7147–7151. [PMC free article] [PubMed] [Google Scholar]
- Yamauchi K, Martinet Y, Crystal RG. Modulation of fibronectin gene expression in human mononuclear phagocytes. J Clin Invest. 1987 Dec;80(6):1720–1727. [PMC free article] [PubMed] [Google Scholar]
- Villiger B, Kelley DG, Engleman W, Kuhn C, 3rd, McDonald JA. Human alveolar macrophage fibronectin: synthesis, secretion, and ultrastructural localization during gelatin-coated latex particle binding. J Cell Biol. 1981 Sep;90(3):711–720. [PMC free article] [PubMed] [Google Scholar]
- Hunninghake GW. Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis. 1984 Apr;129(4):569–572. [PubMed] [Google Scholar]
- Wewers MD, Saltini C, Sellers S, Tocci MJ, Bayne EK, Schmidt JA, Crystal RG. Evaluation of alveolar macrophages in normals and individuals with active pulmonary sarcoidosis for the spontaneous expression of the interleukin-1 beta gene. Cell Immunol. 1987 Jul;107(2):479–488. [PubMed] [Google Scholar]
- Martinet Y, Rom WN, Grotendorst GR, Martin GR, Crystal RG. Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. N Engl J Med. 1987 Jul 23;317(4):202–209. [PubMed] [Google Scholar]
- Pledger WJ, Stiles CD, Antoniades HN, Scher CD. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481–4485. [PMC free article] [PubMed] [Google Scholar]
- Pledger WJ, Stiles CD, Antoniades HN, Scher CD. An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2839–2843. [PMC free article] [PubMed] [Google Scholar]
- Bitterman PB, Rennard SI, Adelberg S, Crystal RG. Role of fibronectin as a growth factor for fibroblasts. J Cell Biol. 1983 Dec;97(6):1925–1932. [PMC free article] [PubMed] [Google Scholar]
- Bitterman PB, Rennard SI, Hunninghake GW, Crystal RG. Human alveolar macrophage growth factor for fibroblasts. Regulation and partial characterization. J Clin Invest. 1982 Oct;70(4):806–822. [PMC free article] [PubMed] [Google Scholar]
- Bitterman PB, Adelberg S, Crystal RG. Mechanisms of pulmonary fibrosis. Spontaneous release of the alveolar macrophage-derived growth factor in the interstitial lung disorders. J Clin Invest. 1983 Nov;72(5):1801–1813. [PMC free article] [PubMed] [Google Scholar]
- Rom WN, Bitterman PB, Rennard SI, Cantin A, Crystal RG. Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts. Am Rev Respir Dis. 1987 Dec;136(6):1429–1434. [PubMed] [Google Scholar]
- Clemmons DR, Underwood LE, Van Wyk JJ. Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts. J Clin Invest. 1981 Jan;67(1):10–19. [PMC free article] [PubMed] [Google Scholar]
- Clemmons DR, Shaw DS. Purification and biologic properties of fibroblast somatomedin. J Biol Chem. 1986 Aug 5;261(22):10293–10298. [PubMed] [Google Scholar]
- Smith EP, Svoboda ME, Van Wyk JJ, Kierszenbaum AL, Tres LL. Partial characterization of a somatomedin-like peptide from the medium of cultured rat Sertoli cells. Endocrinology. 1987 Jan;120(1):186–193. [PubMed] [Google Scholar]
- Rotwein P. Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc Natl Acad Sci U S A. 1986 Jan;83(1):77–81. [PMC free article] [PubMed] [Google Scholar]
- Rotwein P, Pollock KM, Didier DK, Krivi GG. Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. J Biol Chem. 1986 Apr 15;261(11):4828–4832. [PubMed] [Google Scholar]
- Han VK, D'Ercole AJ, Lund PK. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science. 1987 Apr 10;236(4798):193–197. [PubMed] [Google Scholar]
- Bitterman P, Rennard S, Schoenberger C, Crystal R. Asbestos stimulates alveolar macrophages to release a factor causing human lung fibroblasts to replicate. Chest. 1981 Jul;80(1 Suppl):38–39. [PubMed] [Google Scholar]
- Rennard SI, Berg R, Martin GR, Foidart JM, Robey PG. Enzyme-linked immunoassay (ELISA) for connective tissue components. Anal Biochem. 1980 May 1;104(1):205–214. [PubMed] [Google Scholar]
- Furlanetto RW, Underwood LE, Van Wyk JJ, D'Ercole AJ. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. 1977 Sep;60(3):648–657. [PMC free article] [PubMed] [Google Scholar]
- Russell WE, Van Wyk JJ, Pledger WJ. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2389–2392. [PMC free article] [PubMed] [Google Scholar]
- Rosenfeld RG, Dollar LA. Characterization of the somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) receptor on cultured human fibroblast monolayers: regulation of receptor concentrations by SM-C/IGF-I and insulin. J Clin Endocrinol Metab. 1982 Sep;55(3):434–440. [PubMed] [Google Scholar]
- Rosenfeld RG, Dollar LA, Conover CA. Density-associated loss of functional receptors for somatomedin-C/insulinlike growth factor I (SM-C/IGF-I) on cultured human fibroblast monolayers. J Cell Physiol. 1984 Nov;121(2):419–424. [PubMed] [Google Scholar]
- HUNTER WM, GREENWOOD FC. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. [PubMed] [Google Scholar]
- Zapf J, Kaufmann U, Eigenmann EJ, Froesch ER. Determination of nonsuppressible insulin-like activity in human serum by a sensitive protein-binding assay. Clin Chem. 1977;23(4):677–682. [PubMed] [Google Scholar]
- Sasaki N, Rees-Jones RW, Zick Y, Nissley SP, Rechler MM. Characterization of insulin-like growth factor I-stimulated tyrosine kinase activity associated with the beta-subunit of type I insulin-like growth factor receptors of rat liver cells. J Biol Chem. 1985 Aug 15;260(17):9793–9804. [PubMed] [Google Scholar]
- Zinn K, DiMaio D, Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. [PubMed] [Google Scholar]
- Clemmons DR, Van Wyk JJ. Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J Clin Invest. 1985 Jun;75(6):1914–1918. [PMC free article] [PubMed] [Google Scholar]
- Zapf J, Schmid C, Froesch ER. Biological and immunological properties of insulin-like growth factors (IGF) I and II. Clin Endocrinol Metab. 1984 Mar;13(1):3–30. [PubMed] [Google Scholar]
- Cook JJ, Haynes KM, Werther GA. Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production. J Clin Invest. 1988 Jan;81(1):206–212. [PMC free article] [PubMed] [Google Scholar]
- Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978 Apr 25;253(8):2769–2776. [PubMed] [Google Scholar]
- Daughaday WH, Hall K, Raben MS, Salmon WD, Jr, van den Brande JL, van Wyk JJ. Somatomedin: proposed designation for sulphation factor. Nature. 1972 Jan 14;235(5333):107–107. [PubMed] [Google Scholar]
- Van Wyk JJ, Svoboda ME, Underwood LE. Evidence from radioligand assays that somatomedin-C and insulin-like growth factor-I are similar to each other and different from other somatomedins. J Clin Endocrinol Metab. 1980 Jan;50(1):206–208. [PubMed] [Google Scholar]
- Tricoli JV, Rall LB, Scott J, Bell GI, Shows TB. Localization of insulin-like growth factor genes to human chromosomes 11 and 12. Nature. 310(5980):784–786. [PubMed] [Google Scholar]
- Jansen M, van Schaik FM, Ricker AT, Bullock B, Woods DE, Gabbay KH, Nussbaum AL, Sussenbach JS, Van den Brande JL. Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature. 1983 Dec 8;306(5943):609–611. [PubMed] [Google Scholar]
- Blum WF, Ranke MB, Bierich JR. Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV. Acta Endocrinol (Copenh) 1986 Feb;111(2):271–284. [PubMed] [Google Scholar]
- Vassilopoulou-Sellin R, Phillips LS. Extraction of somatomedin activity from rat liver. Endocrinology. 1982 Feb;110(2):582–589. [PubMed] [Google Scholar]
- Froesch ER, Schmid C, Schwander J, Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. [PubMed] [Google Scholar]
- Morell B, Froesch ER. Fibroblasts as an experimental tool in metabolic and hormone studies. II. Effects of insulin and nonsuppressible insulin-like activity (NSILA-S) on fibroblasts in culture. Eur J Clin Invest. 1973 Mar;3(2):119–123. [PubMed] [Google Scholar]
- Conover CA, Rosenfeld RG, Hintz RL. Hormonal control of the replication of human fetal fibroblasts: role of somatomedin C/insulin-like growth factor I. J Cell Physiol. 1986 Jul;128(1):47–54. [PubMed] [Google Scholar]
- Vetter U, Zapf J, Heit W, Helbing G, Heinze E, Froesch ER, Teller WM. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth. J Clin Invest. 1986 Jun;77(6):1903–1908. [PMC free article] [PubMed] [Google Scholar]
- Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk JJ, Pledger WJ. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279–1283. [PMC free article] [PubMed] [Google Scholar]
- Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. [PMC free article] [PubMed] [Google Scholar]
- Jacobs S, Kull FC, Jr, Earp HS, Svoboda ME, Van Wyk JJ, Cuatrecasas P. Somatomedin-C stimulates the phosphorylation of the beta-subunit of its own receptor. J Biol Chem. 1983 Aug 25;258(16):9581–9584. [PubMed] [Google Scholar]
- Massagué J, Czech MP. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem. 1982 May 10;257(9):5038–5045. [PubMed] [Google Scholar]
- Rechler MM, Nissley SP. The nature and regulation of the receptors for insulin-like growth factors. Annu Rev Physiol. 1985;47:425–442. [PubMed] [Google Scholar]
- Nissley SP, Rechler MM. Somatomedin/insulin-like growth factor tissue receptors. Clin Endocrinol Metab. 1984 Mar;13(1):43–67. [PubMed] [Google Scholar]
- Ong J, Yamashita S, Melmed S. Insulin-like growth factor I induces c-fos messenger ribonucleic acid in L6 rat skeletal muscle cells. Endocrinology. 1987 Jan;120(1):353–357. [PubMed] [Google Scholar]
- Mathews LS, Norstedt G, Palmiter RD. Regulation of insulin-like growth factor I gene expression by growth hormone. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9343–9347. [PMC free article] [PubMed] [Google Scholar]
- Merimee TJ, Zapf J, Hewlett B, Cavalli-Sforza LL. Insulin-like growth factors in pygmies. The role of puberty in determining final stature. N Engl J Med. 1987 Apr 9;316(15):906–911. [PubMed] [Google Scholar]
- De Troyer A, Desir D, Copinschi G. Regression of lung size in adults with growth hormone deficiency. Q J Med. 1980;49(195):329–340. [PubMed] [Google Scholar]
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