Exaggerated Spontaneous Release of Platelet-Derived Growth Factor by Alveolar Macrophages from Patients with Idiopathic Pulmonary Fibrosis

Yves Martinet, William N. Rom, Gary R. Grotendorst, George R. Martin, Ronald G. Crystal

Research output: Contribution to journalArticle

258 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P<0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a “competence” factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract. (N Engl J Med 1987; 317: 202–9.) BOTH normal tissue repair and the pathologic fibrosis of normal organs are intimately linked to processes that recruit mesenchymal cells and stimulate them to proliferate at local sites. Since mesenchymal cells produce and secrete the principal components of scar tissue, the recruitment and proliferation of mesenchymal cells form the basis of normal tissue repair, and the exaggerated recruitment and proliferation of mesenchymal cells after extensive tissue damage represent a fundamental mechanism in the pathogenesis of tissue fibrosis.1 2 3 Although mesenchymal cells have the innate ability to migrate and proliferate, they are usually quiescent unless they encounter external mediators4 5 6 7 8 that signal them.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalNew England Journal of Medicine
Volume317
Issue number4
DOIs
Publication statusPublished - 23 Jul 1987

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this