Prolonged inhibition of obliterative airway disease in murine tracheal allografts by brief treatment with anti-leukocyte function-associated antigen-1 (CD11a) monoclonal antibody.
BACKGROUND
We have previously shown that anti-leukocyte function-associated antigen (LFA)-1 (CD11a) monoclonal antibody (mAb) prevents acute rejection and produces donor-specific unresponsiveness in murine recipients of heterotopic heart allografts. Here, we investigate the ability of this mAb to prevent the development of obliterative airway disease (OAD) in murine recipients of tracheal allografts.


RESULTS
BALB/c tracheae were heterotopically transplanted into C3H mice. OAD developed by day 28 after transplantation and was characterized histologically by a loss of epithelial cell coverage and luminal obliteration of the tracheal allograft with a proliferation of fibrogenic mesenchymal cells, which is a lesion comparable to obliterative bronchiolitis in human lung transplant recipients. Monotherapy with anti-LFA-1 mAb preserved graft epithelium, prevented the development of OAD, and maintained unresponsiveness to donor antigen for more than 42 days after the final mAb administration.


CONCLUSIONS
These findings suggest the potential for anti-LFA-1 mAb therapy to suppress both acute and chronic rejection in clinical lung transplantation.
Morikawa
M
M
Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA 94305-5407, USA.
Brazelton
T R
TR
Berry
G J
GJ
Morris
R E
RE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D014133:Tracheal Diseases / Q000517:prevention & control*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1