An animal model of autoimmune emphysema.
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.
Taraseviciene-Stewart
Laimute
L
Department of Medicine, Division of Pulmonary Sciences, UCHSC, 4200 East Ninth Ave, C272, Denver, CO 80262, USA.
Scerbavicius
Robertas
R
Choe
Kang-Hyeon
KH
Moore
Melissa
M
Sullivan
Andrew
A
Nicolls
Mark R
MR
Fontenot
Andrew P
AP
Tuder
Rubin M
RM
Voelkel
Norbert F
NF
D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D008297:Male; D011656:Pulmonary Emphysema / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
D001323:Autoantibodies