PMID- 9233699
OWN - NLM
STAT- MEDLINE
DCOM- 19970813
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 64
IP  - 1
DP  - 1997 Jul 15
TI  - Mechanism of concordant corneal xenograft rejection in mice: synergistic effects 
      of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.
PG  - 42-8
AB  - BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the 
      potential role of immunosuppressive therapy in the suppression of corneal 
      xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who 
      received orthotopic corneal transplants (Lewis rats donors) were administered 
      intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal 
      antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during 
      a 12-day postoperative period. Histological (hematoxylin-eosin stain) and 
      immunohistochemical evaluations of enucleated eyes were performed. Humoral immune 
      response and delayed-type hypersensitivity (ear-swelling assay) were evaluated. 
      RESULTS: The mean (+/-SD) graft survival time in the untreated control, 
      FK506-treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 
      5.8+/-0.8, 9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the 
      untreated control group, mouse IgG, IgM, and C3 were expressed on the rat corneal 
      grafts during the early postoperative phase. Flow cytometry studies revealed high 
      titers of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were 
      expressed on xenografted corneal beds, and delayed-type hypersensitivity was 
      induced. However, local expression of IgM, C3 and T helper 1 cytokines, serum 
      antibodies of IgG and IgM, and delayed-type hypersensitivity were suppressed in 
      the anti-LFA-1 mAb- plus FK506-treated group. CONCLUSIONS: Both humoral and 
      cell-mediated immune reaction play an important role in the initial rejection in 
      rat-to-mouse corneal xenotransplantation. The treatment with anti-LFA-1 mAb in 
      combination with FK506 synergistically suppresses concordant corneal xenogeneic 
      reaction.
FAU - Yamagami, S
AU  - Yamagami S
AD  - Department of Ophthalmology, Jichi Medical School, Kawachi-gun, Tochigi, Japan.
FAU - Isobe, M
AU  - Isobe M
FAU - Yamagami, H
AU  - Yamagami H
FAU - Hori, J
AU  - Hori J
FAU - Tsuru, T
AU  - Tsuru T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Lymphocyte Function-Associated Antigen-1)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antibody Formation
MH  - Antibody Specificity
MH  - Corneal Transplantation/*immunology
MH  - Drug Synergism
MH  - Graft Rejection/prevention & control
MH  - Graft Survival/drug effects/immunology
MH  - Hypersensitivity, Delayed/immunology
MH  - Immunity, Cellular
MH  - Immunohistochemistry
MH  - Lymphocyte Function-Associated Antigen-1/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Spleen/cytology
MH  - Tacrolimus/pharmacology
MH  - Transplantation, Heterologous/*immunology
EDAT- 1997/07/15 00:00
MHDA- 1997/07/15 00:01
CRDT- 1997/07/15 00:00
PHST- 1997/07/15 00:00 [pubmed]
PHST- 1997/07/15 00:01 [medline]
PHST- 1997/07/15 00:00 [entrez]
AID - 10.1097/00007890-199707150-00009 [doi]
PST - ppublish
SO  - Transplantation. 1997 Jul 15;64(1):42-8. doi: 10.1097/00007890-199707150-00009.