A CD36 synthetic peptide inhibits bleomycin-induced pulmonary inflammation and connective tissue synthesis in the rat

Am J Respir Cell Mol Biol. 2000 Aug;23(2):204-12. doi: 10.1165/ajrcmb.23.2.4089.


Transforming growth factor (TGF)-beta1 is an important regulator of inflammation and fibrosis. TGF-beta1 is usually secreted as a biologically latent protein called latent TGF-beta1 (L-TGF-beta1). L-TGF-beta1 has no biologic effect unless L-TGF-beta1 is converted to its active form. Using a well-recognized model of lung injury induced by the antineoplastic antibiotic bleomycin (Blm), we demonstrated that 7 d after intratracheal Blm administration, total lung TGF-beta was maximally increased. This induction was due to TGF-beta1 production by alveolar macrophages that, when explanted, generated increased quantities of L-TGF-beta1 complexed with the glycoprotein thrombospondin (TSP)-1. The TSP-1/L-TGF-beta1 complex was associated with CD36, a receptor for TSP-1. The association of TSP-1/L-TGF-beta1 to CD36 was critical for plasmin-mediated release of mature TGF-beta1. In this paper we show that, compared with administration of Blm by itself, when a synthetic peptide of CD36 between amino acids 93 and 110 is given concomitantly with Blm to rats, alveolar macrophages generate markedly less active TGF-beta1, the rats gain weight more rapidly, and there is less inflammation, collagen I and III, and fibronectin synthesis. These findings demonstrate a novel in vivo mechanism of activation of L-TGF-beta1 in lung injury and the importance of alveolar macrophage- derived active TGF-beta1 in the pathogenesis of pulmonary inflammation and fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / adverse effects*
  • Body Weight / drug effects
  • Bronchoalveolar Lavage Fluid / cytology
  • CD36 Antigens / chemistry
  • CD36 Antigens / pharmacology*
  • Cell Count / drug effects
  • Cell Survival / drug effects
  • Collagen / drug effects
  • Collagen / metabolism
  • Connective Tissue / chemistry
  • Connective Tissue / drug effects*
  • Connective Tissue / metabolism
  • Decorin
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / drug effects*
  • Female
  • Fibronectins / drug effects
  • Fibronectins / metabolism
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Diseases / chemically induced
  • Lung Diseases / prevention & control*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Oligopeptides / pharmacology
  • Proteoglycans / drug effects
  • Proteoglycans / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / metabolism
  • Tumor Cells, Cultured


  • CD36 Antigens
  • Dcn protein, rat
  • Decorin
  • Extracellular Matrix Proteins
  • Fibronectins
  • Oligopeptides
  • Proteoglycans
  • Transforming Growth Factor beta
  • Bleomycin
  • Collagen