Acute lung injury. Pathogenesis of intraalveolar fibrosis.
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Journal: 1991/September - Journal of Clinical Investigation
ISSN: 0021-9738
Abstract:
In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.
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J Clin Invest 88(2): 663-673
PMID: 1864975

Acute lung injury. Pathogenesis of intraalveolar fibrosis.

Abstract

In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.

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Selected References

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  • Rinaldo JE, Rogers RM. Adult respiratory-distress syndrome: changing concepts of lung injury and repair. N Engl J Med. 1982 Apr 15;306(15):900–909. [PubMed] [Google Scholar]
  • McGuire WW, Spragg RG, Cohen AB, Cochrane CG. Studies on the pathogenesis of the adult respiratory distress syndrome. J Clin Invest. 1982 Mar;69(3):543–553.[PMC free article] [PubMed] [Google Scholar]
  • Petty TL, Ashbaugh DG. The adult respiratory distress syndrome. Clinical features, factors influencing prognosis and principles of management. Chest. 1971 Sep;60(3):233–239. [PubMed] [Google Scholar]
  • Fowler AA, Hamman RF, Zerbe GO, Benson KN, Hyers TM. Adult respiratory distress syndrome. Prognosis after onset. Am Rev Respir Dis. 1985 Sep;132(3):472–478. [PubMed] [Google Scholar]
  • Schraufstätter IU, Revak SD, Cochrane CG. Proteases and oxidants in experimental pulmonary inflammatory injury. J Clin Invest. 1984 Apr;73(4):1175–1184.[PMC free article] [PubMed] [Google Scholar]
  • Fantone JC, Ward PA. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982 Jun;107(3):395–418.[PMC free article] [PubMed] [Google Scholar]
  • Kaplan RL, Sahn SA, Petty TL. Incidence and outcome of the respiratory distress syndrome in gram-negative sepsis. Arch Intern Med. 1979 Aug;139(8):867–869. [PubMed] [Google Scholar]
  • Rotman HH, Lavelle TF, Jr, Dimcheff DG, VandenBelt RJ, Weg JG. Long-term physiologic consequences of the adult respiratory distress syndrome. Chest. 1977 Aug;72(2):190–192. [PubMed] [Google Scholar]
  • Bachofen M, Weibel ER. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis. 1977 Oct;116(4):589–615. [PubMed] [Google Scholar]
  • Kapanci Y, Weibel ER, Kaplan HP, Robinson FR. Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies. Lab Invest. 1969 Jan;20(1):101–118. [PubMed] [Google Scholar]
  • Haschek WM, Reiser KM, Klein-Szanto AJ, Kehrer JP, Smith LH, Last JA, Witschi HP. Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism. Am Rev Respir Dis. 1983 Jan;127(1):28–34. [PubMed] [Google Scholar]
  • Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y. The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol. 1987 Jan;126(1):171–182.[PMC free article] [PubMed] [Google Scholar]
  • Katzenstein AL, Myers JL, Mazur MT. Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. Am J Surg Pathol. 1986 Apr;10(4):256–267. [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]
  • Saltini C, Hance AJ, Ferrans VJ, Basset F, Bitterman PB, Crystal RG. Accurate quantification of cells recovered by bronchoalveolar lavage. Am Rev Respir Dis. 1984 Oct;130(4):650–658. [PubMed] [Google Scholar]
  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. [PubMed] [Google Scholar]
  • Davis WB, Rennard SI, Bitterman PB, Crystal RG. Pulmonary oxygen toxicity. Early reversible changes in human alveolar structures induced by hyperoxia. N Engl J Med. 1983 Oct 13;309(15):878–883. [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]
  • 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]
  • 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]
  • Ham RG. Dermal fibroblasts. Methods Cell Biol. 1980;21A:255–276. [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]
  • Barnes D, Sato G. Serum-free cell culture: a unifying approach. Cell. 1980 Dec;22(3):649–655. [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]
  • 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]
  • 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]
  • Heldin CH, Johnsson A, Ek B, Wennergren S, Rönnstrand L, Hammacher A, Faulders B, Wasteson A, Westermark B. Purification of human platelet-derived growth factor. Methods Enzymol. 1987;147:3–13. [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]
  • Mariash CN, Seelig S, Oppenheimer JH. A rapid, inexpensive, quantitative technique for the analysis of two-dimensional electrophoretograms. Anal Biochem. 1982 Apr;121(2):388–394. [PubMed] [Google Scholar]
  • Holter JF, Weiland JE, Pacht ER, Gadek JE, Davis WB. Protein permeability in the adult respiratory distress syndrome. Loss of size selectivity of the alveolar epithelium. J Clin Invest. 1986 Dec;78(6):1513–1522.[PMC free article] [PubMed] [Google Scholar]
  • Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986 Feb;133(2):218–225. [PubMed] [Google Scholar]
  • Matsuoka J, Grotendorst GR. Two peptides related to platelet-derived growth factor are present in human wound fluid. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4416–4420.[PMC free article] [PubMed] [Google Scholar]
  • Raines EW, Ross R. Purification of human platelet-derived growth factor. Methods Enzymol. 1985;109:749–773. [PubMed] [Google Scholar]
  • Heldin CH, Westermark B, Wasteson A. Platelet-derived growth factor. Isolation by a large-scale procedure and analysis of subunit composition. Biochem J. 1981 Mar 1;193(3):907–913.[PMC free article] [PubMed] [Google Scholar]
  • Deuel TF, Huang JS, Proffitt RT, Baenziger JU, Chang D, Kennedy BB. Human platelet-derived growth factor. Purification and resolution into two active protein fractions. J Biol Chem. 1981 Sep 10;256(17):8896–8899. [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]
  • 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]
  • 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]
  • Pencev D, Grotendorst GR. Human peripheral blood monocytes secrete a unique form of PDGF. Oncogene Res. 1988;3(4):333–342. [PubMed] [Google Scholar]
  • Harlan JM, Thompson PJ, Ross RR, Bowen-Pope DF. Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells. J Cell Biol. 1986 Sep;103(3):1129–1133.[PMC free article] [PubMed] [Google Scholar]
  • Gajdusek C, Carbon S, Ross R, Nawroth P, Stern D. Activation of coagulation releases endothelial cell mitogens. J Cell Biol. 1986 Aug;103(2):419–428.[PMC free article] [PubMed] [Google Scholar]
  • Collins T, Ginsburg D, Boss JM, Orkin SH, Pober JS. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature. 1985 Aug 22;316(6030):748–750. [PubMed] [Google Scholar]
  • Paulsson Y, Hammacher A, Heldin CH, Westermark B. Possible positive autocrine feedback in the prereplicative phase of human fibroblasts. Nature. 1987 Aug 20;328(6132):715–717. [PubMed] [Google Scholar]
  • Libby P, Warner SJ, Salomon RN, Birinyi LK. Production of platelet-derived growth factor-like mitogen by smooth-muscle cells from human atheroma. N Engl J Med. 1988 Jun 9;318(23):1493–1498. [PubMed] [Google Scholar]
  • Raines EW, Bowen-Pope DF, Ross R. Plasma binding proteins for platelet-derived growth factor that inhibit its binding to cell-surface receptors. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3424–3428.[PMC free article] [PubMed] [Google Scholar]
  • Huang JS, Huang SS, Deuel TF. Specific covalent binding of platelet-derived growth factor to human plasma alpha 2-macroglobulin. Proc Natl Acad Sci U S A. 1984 Jan;81(2):342–346.[PMC free article] [PubMed] [Google Scholar]
  • Robbins KC, Antoniades HN, Devare SG, Hunkapiller MW, Aaronson SA. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature. 1983 Oct 13;305(5935):605–608. [PubMed] [Google Scholar]
  • DiCorleto PE. Cultured endothelial cells produce multiple growth factors for connective tissue cells. Exp Cell Res. 1984 Jul;153(1):167–172. [PubMed] [Google Scholar]
  • Campochiaro PA, Sugg R, Grotendorst G, Hjelmeland LM. Retinal pigment epithelial cells produce PDGF-like proteins and secrete them into their media. Exp Eye Res. 1989 Aug;49(2):217–227. [PubMed] [Google Scholar]
  • Soma Y, Grotendorst GR. TGF-beta stimulates primary human skin fibroblast DNA synthesis via an autocrine production of PDGF-related peptides. J Cell Physiol. 1989 Aug;140(2):246–253. [PubMed] [Google Scholar]
Department of Medicine, University of Minnesota, Minneapolis 55455.
Department of Medicine, University of Minnesota, Minneapolis 55455.
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Abstract
In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.
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