Document Detail

Effects of the immunosuppressant FK506 on a penetrating keratoplasty rejection model in the rat.
MedLine Citation:
PMID:  7686893     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model. METHODS: Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry. RESULTS: The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas. CONCLUSIONS: These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.
M Nishi; C P Herbort; M Matsubara; Y Morishita; M Nishimura; M Nieda; S Mori; M Mochizuki
Related Documents :
20580263 - Cardiomyocyte-targeted hif-1alpha gene therapy inhibits cardiomyocyte apoptosis and car...
7686893 - Effects of the immunosuppressant fk506 on a penetrating keratoplasty rejection model in...
8789893 - Changes in jejunal mucosa after long-term feeding of germfree rats with gluten.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  34     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-12     Completed Date:  1993-08-12     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2477-86     Citation Subset:  IM    
Department of Ophthalmology, Escola Paulista de Medicina, S?o Paulo, Brazil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cells, Cultured
Cornea / drug effects*,  immunology,  pathology
Disease Models, Animal
Graft Rejection / immunology,  pathology,  prevention & control*
Graft Survival / drug effects,  immunology
Histocompatibility Antigens Class II / immunology
Immunoenzyme Techniques
Keratoplasty, Penetrating / immunology*,  pathology
Lymphocyte Culture Test, Mixed
Rats, Inbred BN
Rats, Inbred F344
Rats, Inbred Lew
Receptors, Interleukin-2 / immunology
Tacrolimus / pharmacology*
Transplantation, Homologous
Reg. No./Substance:
0/Histocompatibility Antigens Class II; 0/Receptors, Interleukin-2; 109581-93-3/Tacrolimus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Leukocyte adhesion molecules in diseased corneas.
Next Document:  A tumor promoter-resistant subpopulation of progenitor cells is larger in limbal epithelium than in ...