TY - JOUR
T1 - Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death
T2 - A possible mechanism for bronchiolitis obliterans syndrome
AU - Jaramillo, Andrés
AU - Smith, Craig R.
AU - Maruyama, Takahiro
AU - Zhang, Leiying
AU - Patterson, G. Alexander
AU - Mohanakumar, T.
N1 - Funding Information:
This work was supported by Grants No. HL56643 and HL66452 from the National Institutes of Health. The authors would like to thank Ms. Billie J. Glasscock for secretarial assistance.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Development of anti-HLA class I antibodies is associated with bronchiolitis obliterans syndrome (BOS) after lung transplantation. BOS is characterized histologically by significant fibrosis and airway epithelial cell (AEC) apoptosis. Thus, this study was designed to determine whether anti-HLA class I antibodies can activate AECs to produce growth factors and to undergo apoptosis. KCC-266 AECs were activated with the W6/32 anti-HLA class I monoclonal antibody. Proliferation and apoptosis levels were determined after 24, 48, and 72 hours. The induction of fibroblast and bronchial smooth muscle cell proliferation by anti-HLA class I activated AECs was assessed in the presence of neutralizing antibodies against various growth factors. The anti-HLA class I induced AEC proliferation after 24 hours followed by significant induction of apoptosis after 48 hours. Anti-HLA class I activated AECs produced soluble growth factors that stimulated fibroblasts but not bronchial smooth muscle cells. The stimulation of fibroblast proliferation was inhibited by antibodies against plateletderived growth factor, heparin-binding epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. The results from this study suggest that anti-HLA class I alloantibodies may play an important role in the pathogenesis of BOS by inducing proliferation, growth factor production, and apoptotic cell death in AECs.
AB - Development of anti-HLA class I antibodies is associated with bronchiolitis obliterans syndrome (BOS) after lung transplantation. BOS is characterized histologically by significant fibrosis and airway epithelial cell (AEC) apoptosis. Thus, this study was designed to determine whether anti-HLA class I antibodies can activate AECs to produce growth factors and to undergo apoptosis. KCC-266 AECs were activated with the W6/32 anti-HLA class I monoclonal antibody. Proliferation and apoptosis levels were determined after 24, 48, and 72 hours. The induction of fibroblast and bronchial smooth muscle cell proliferation by anti-HLA class I activated AECs was assessed in the presence of neutralizing antibodies against various growth factors. The anti-HLA class I induced AEC proliferation after 24 hours followed by significant induction of apoptosis after 48 hours. Anti-HLA class I activated AECs produced soluble growth factors that stimulated fibroblasts but not bronchial smooth muscle cells. The stimulation of fibroblast proliferation was inhibited by antibodies against plateletderived growth factor, heparin-binding epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. The results from this study suggest that anti-HLA class I alloantibodies may play an important role in the pathogenesis of BOS by inducing proliferation, growth factor production, and apoptotic cell death in AECs.
KW - Airway epithelial cells
KW - Apoptosis
KW - Bronchiolitis obliterans syndrome
KW - Growth factors
KW - Lung transplantation
UR - http://www.scopus.com/inward/record.url?scp=0037405289&partnerID=8YFLogxK
U2 - 10.1016/S0198-8859(03)00038-7
DO - 10.1016/S0198-8859(03)00038-7
M3 - Article
C2 - 12691702
AN - SCOPUS:0037405289
SN - 0198-8859
VL - 64
SP - 521
EP - 529
JO - Human Immunology
JF - Human Immunology
IS - 5
ER -