Increased iNOS-expressing macrophage in long-term surviving rat small-bowel grafts

Li, Xiaosong; Chen, Yan; Tian, Lina; Lui, Vincent C.H.; Tam, Paul K.H.

doi:10.1016/j.amjsurg.2006.09.032

« Previous Next »The American Journal of Surgery
Volume 194, Issue 2 , Pages 248-254, August 2007

Increased iNOS-expressing macrophage in long-term surviving rat small-bowel grafts

Xiaosong Li, Ph.D.
- Current address: Department of Surgery, Beijing Children’s Hospital, Affiliated Capital University of Medical Sciences, Nan Lishi Rd., Beijing 100045, PRC
- Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC
Yan Chen, Ph.D.
- Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC
Lina Tian, Ph.D.
- Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC
- Current address: Department of Surgery, Central Clinical School, The University of Sydney, Sydney, NSW 2006 Australia
Vincent C.H. Lui, Ph.D.
- Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC
Paul K.H. Tam, M.D.
- Division of Pediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC
- Corresponding author. Tel.: +011-852-28554850; fax: +011852-28173155.

Received 30 May 2006; received in revised form 26 September 2006 published online 31 March 2007.

Abstract

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.

Comments

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.

Keywords: Chronic rejection, Fibrosis, FK506, rapamycin, Vasculopathy