An animal model of autoimmune emphysema

Am J Respir Crit Care Med. 2005 Apr 1;171(7):734-42. doi: 10.1164/rccm.200409-1275OC. Epub 2004 Nov 24.


Although cigarette smoking is implicated in the pathogenesis of emphysema, the precise mechanisms of chronic progressive alveolar septal destruction are not well understood. We show, in a novel animal model, that immunocompetent, but not athymic, nude rats injected intraperitoneally with xenogeneic endothelial cells (ECs) produce antibodies against ECs and develop emphysema. Immunization with ECs also leads to alveolar septal cell apoptosis and activation of matrix metalloproteases MMP-9 and MMP-2. Anti-EC antibodies cause EC apoptosis in vitro and emphysema in passively immunized mice. Moreover, immunization also causes accumulation of CD4+ T cells in the lung. Adoptive transfer of pathogenic, spleen-derived CD4+ cells into naive immunocompetent animal also results in emphysema. This study shows for the first time that humoral- and CD4+ cell-dependent mechanisms are sufficient to trigger the development of emphysema, suggesting that alveolar septal cell destruction might result from immune mechanisms.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Apoptosis / physiology
  • Autoantibodies / analysis
  • Autoantibodies / immunology*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Cells
  • Enzyme-Linked Immunosorbent Assay
  • In Situ Nick-End Labeling
  • Male
  • Pulmonary Emphysema / immunology*
  • Pulmonary Emphysema / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Sensitivity and Specificity


  • Autoantibodies