Increased iNOS-expressing macrophage in long-term surviving rat small-bowel grafts.
BACKGROUND
Inducible nitric oxide synthase (iNOS) produces nitric oxide and modulates many biologic processes critical in the development of rejection; however, its role in chronic rejection (CR) in small-bowel transplantation (SBT) is largely unknown.


METHODS
FK506 prevented acute rejection (AR); however, recipients eventually lost their bowel grafts to CR. Combined FK506 and rapamycin treatment prevented CR, thus leading to long-term graft survival. We investigated iNOS expression in our rat orthotopic SBT CR model.


RESULTS
Histologically, mesentery vascular occlusion and fibrosis, which are hallmarks of CR, were apparent in bowel grafts in an FK506 single-treatment group. In contrast, patients with long-term surviving grafts receiving FK506 and rapamycin developed mild vascular occlusion and fibrosis. Unlike in AR, low iNOS expression, which is associated with decreased macrophage infiltration, was observed in CR grafts. However, iNOS expression and macrophage infiltration was higher in long-term-surviving grafts than CR grafts. Immunofluorescence staining revealed that the majority of macrophages expressed iNOS in long-term surviving grafts.


CONCLUSIONS
Sequential treatment combining FK506 and rapamycin prolonged survival of SBT animals with decreased vasculopathy and collagen deposition of the intestinal grafts. iNOS may play opposing roles in AR and CR in SBT.
Li
Xiaosong
X
Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.
Chen
Yan
Y
Tian
Lina
L
Lui
Vincent C H
VC
Tam
Paul K H
PK
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007421:Intestine, Small / Q000201:enzymology* / Q000473:pathology / Q000637:transplantation*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage
D007166:Immunosuppressive Agents; D052247:Nitric Oxide Synthase Type II; D020123:Sirolimus; D016559:Tacrolimus