Pathogenesis of pulmonary fibrosis: platelet-derived growth factor precedes structural alterations in the Hermansky-Pudlak syndrome.

Peptides that modulate mesenchymal cell function have been detected in the fibrotic lung disorders once physiologic dysfunction is present. Despite this close association with manifest disease, their role in initiating alveolar remodeling remains unknown. We examined the hypothesis that one potent peptide, platelet-derived growth factor (PDGF), would be present at the alveolar surface before the onset of physiologic dysfunction in patients in whom pulmonary fibrosis subsequently develops. Bronchoalveolar lavage and physiologic assessment were performed in asymptomatic patients with the Hermansky-Pudlak syndrome (n = 30), obligate heterozygous (n = 9), and normal volunteers (control group). Lavage cell number and profile were normal, but alveolar macrophages demonstrated characteristic autofluorescence and ultrastructural features of ceroid. Lavage fluid from physiologically normal patients with Hermansky-Pudlak syndrome and from those with occult restrictive disease demonstrated two PDGF-related peptides (14 kd and 38 kd). Radioligand binding and fibroblast proliferation assay demonstrated that the peptides were functional. By immunoassay the concentration of PDGF in lavage fluid was six times greater than control values (p < 0.01). In situ hybridization together with bioassay indicated that alveolar macrophages were one cellular source of PDGF. Similar results were obtained for heterozygotes. These data identify macrophage-derived PDGF peptides as important candidate molecules in the initiation of alveolar remodeling in the fibrotic lung disorders.
AuthorsK R Harmon, C J Witkop, J G White, R A King, M Peterson, D Moore, J Tashjian, W A Marinelli, P B Bitterman
JournalThe Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 123 Issue 4 Pg. 617-27 (Apr 1994) ISSN: 0022-2143 [Print] UNITED STATES
PMID8145011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Platelet-Derived Growth Factor
  • Adolescent
  • Adult
  • Albinism, Oculocutaneous (complications, genetics, metabolism, pathology)
  • Base Sequence
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid
  • Female
  • Heterozygote
  • Humans
  • In Situ Hybridization
  • Macrophages, Alveolar (metabolism)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Platelet-Derived Growth Factor (physiology)
  • Pulmonary Fibrosis (etiology, metabolism)
  • Radioligand Assay

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