PMID- 11472629
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20211203
IS  - 0908-665X (Print)
IS  - 0908-665X (Linking)
VI  - 8
IP  - 3
DP  - 2001 Aug
TI  - Hamster-to-rat bone marrow xenotransplantation and humoral graft vs. host 
      disease.
PG  - 213-21
AB  - Bone marrow transplantation (BMT) may induce tolerance across xenogeneic 
      barriers. We have established a xenogeneic BMT model where hamster BM is 
      transplanted into splenectomized LEW rat recipients resulting in high levels of 
      engraftment. Unfortunately, graft vs. host disease (GVHD) with severe dermatitis 
      developed in all rat recipients. We were successful in treating or preventing the 
      dermatitis of this xenogeneic GVHD by the use of the T-cell suppressant 
      tacrolimus. However, this compound did not prevent the development of a fatal 
      liver injury in the rat recipients. This study was designed to elucidate the 
      pathogenesis of this liver injury appearing in T-cell suppressed rat recipients 
      of hamster BM. Splenectomized and irradiated (10 Gy) LEW rats received 300 x 106 
      unfractionated hamster BM cells. These BMT recipients were divided in 3 groups: 
      Group I recipients (n = 8) did not receive further immunosuppression. Group II 
      animals (n = 10) received tacrolimus 1 mg/kg/d for 7 d. Group III recipients (n = 
      6) were given the same daily dose of tacrolimus on a long-term basis. Chimerism 
      was detected by flow cytometry. Cytotoxicity of recipient's sera against rat and 
      hamster lymph node cells was measured by complement-dependent cytotoxicity (CDC) 
      test. Immunofluorescence was used to detect hamster antirat antibodies on several 
      recipient organs. In Group I, 2 out of 8 animals engrafted (25%) and survived for 
      a median of 21 d showing the severe dermatitis characteristic of GVHD. In group 
      II (n = 10), 9/10 rat recipients engrafted (90%) and survival was increased to a 
      median of 53.7 days. However, these surviving recipients developed fatal GVHD not 
      different from that observed in Group I recipients. All animals in Group III (n = 
      6) engrafted and did not show the characteristic dermatitis of GVHD. Their 
      survival, however, was shortened to a median of 30.3 d by a severe liver injury. 
      This injury was characterized by hepatocyte necrosis in zones 1 and 2 with 
      polymorphonuclear (PMN) cell infiltration. Deposits of hamster immunoglobulins 
      were present around the necrotic areas and in the portal veins. Moreover, antirat 
      antibodies appeared in the circulation. These antibodies were sensitive to 
      dithiothreitol (DTT) treatment indicating that they were of the IgM class. This 
      study shows that xenogeneic GVHD may have a dual presentation in the 
      hamster-to-rat model: a classical cellular GVHD not distinct to the allogeneic 
      one and a humoral GVHD affecting solely the recipient liver. The degree of 
      humoral injury is potentiated by T-cell suppression.
FAU - Miki, T
AU  - Miki T
AD  - Thomas E. Starzl Transplantation Institute and the Department of Surgery, 
      University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
FAU - Lee, Y H
AU  - Lee YH
FAU - Tandin, A
AU  - Tandin A
FAU - Subbotin, V
AU  - Subbotin V
FAU - Goller, A
AU  - Goller A
FAU - Kovscek, A
AU  - Kovscek A
FAU - Fung, J J
AU  - Fung JJ
FAU - Valdivia, L A
AU  - Valdivia LA
LA  - eng
GR  - DK29961/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Denmark
TA  - Xenotransplantation
JT  - Xenotransplantation
JID - 9438793
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*immunology
MH  - Cricetinae
MH  - Flow Cytometry
MH  - Graft Survival/*immunology
MH  - Graft vs Host Disease/*immunology
MH  - Immunosuppression Therapy/methods
MH  - Male
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Splenectomy
MH  - Tacrolimus/pharmacology
MH  - Transplantation Chimera
MH  - Transplantation, Heterologous/*immunology
EDAT- 2001/07/27 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/07/27 10:00
PHST- 2001/07/27 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/07/27 10:00 [entrez]
AID - xen112 [pii]
AID - 10.1034/j.1399-3089.2001.0o112.x [doi]
PST - ppublish
SO  - Xenotransplantation. 2001 Aug;8(3):213-21. doi: 10.1034/j.1399-3089.2001.0o112.x.