Obliterative bronchiolitis after lung transplantation: A fibroproliferative disorder associated with platelet-derived growth factor

Marshall I. Hertz, Craig A. Henke, Raouf E. Nakhleh, Keith R. Harmon, William A. Marinelli, Joan M.K. Fox, Spencer H. Kubo, Sara J. Shumway, R. Morton Bolman, Peter B. Bitterman

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative bronchiolitis patients (patients, 104 ± 26.9 pM; controls, 8.4 ± 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative bronchiolitis.

Original languageEnglish (US)
Pages (from-to)10385-10389
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number21
DOIs
StatePublished - 1992

Keywords

  • In situ hybridization
  • Organ transplantation

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