Linking inflammation to acute rejection in small-for-size liver allografts: the potential role of early macrophage activation

Am J Transplant. 2004 Feb;4(2):196-209. doi: 10.1046/j.1600-6143.2003.00313.x.


This study aims to investigate the immunological status of small-for-size liver allografts and possible mechanism that contributes to the accelerated immune response in these allografts. Eight experimental groups were: whole isografts; 40% isografts; whole allografts, no treatment; 40% allografts, no treatment; whole allografts with sodium salicylate intraperitoneal injection, D0-3; 40% allografts with sodium salicylate, D0-3; whole allografts with FK506 intramuscular injection D0-3, and 40% allografts with FK506, D0-3. The 40% allografts survived significantly shorter than whole allografts (p=0.02). At 72 h after reperfusion, a higher number of macrophages infiltrated into the periportal area of small-for-size allografts than whole allografts. Remarkable up-regulation of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) messenger RNA (mRNA) levels were detected in small-for-size allografts within 24 h after reperfusion. Sodium salicylate administration reduced IL-1beta and IFN-gamma mRNA in both small-for-size and whole allografts, but it could decrease IL-2 and IL-10 mRNA levels only in small-for-size allografts. In vitro study revealed that CD80, CD86 and CD11b expression on macrophages was augmented after IL-1beta stimulation, whereas the up-regulation could be blocked by sodium salicylate. In conclusion, early activation of macrophages as a result of graft injury might play an important role in the accelerated acute rejection process in small-for-size allografts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Graft Rejection / immunology
  • Graft Rejection / pathology*
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Inflammation / immunology
  • Inflammation / pathology*
  • Liver / anatomy & histology*
  • Liver Transplantation / immunology*
  • Liver Transplantation / pathology
  • Macrophage Activation / immunology*
  • Male
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred Lew
  • Rats, Inbred Strains
  • Transplantation, Homologous
  • Transplantation, Isogeneic


  • RNA, Messenger