title: Preconditioning donor livers with cromolyn or compound 48/80 prolongs recipient survival in a rat orthotopic liver transplantation model.
abstract: BACKGROUND
  Acute rejection (AR) remains a challenge in organ transplantation. Preconditioning donor organs can reduce AR and prolong survival. Whether preconditioning with cromolyn (CRM), a mast cell (MC) stabilizer, or compound 48/80 (CMP 48/80), a MC degranulator, can alleviate AR and prolong survival has not been studied.
  
  
  METHODS
  We used the male-DA-to-female-Lewis-rat orthotopic liver transplantation (OLT) model. Donors were preconditioned with CRM in a MC stabilizing way (CRM group) or CMP 48/80 in a MC depleting way (CMP 48/80 group). Rats preconditioned with phosphate-buffered saline were used as controls (PBS group). After preconditioning, OLT surgeries were carried out. OLT male-Lewis-to-female-Lewis-rats were used as the syngeneic group (syngeneic group).
  
  
  RESULTS
  Rats in the PBS group developed AR rapidly and died at 7.40 ± 1.14 days. Rats in the CRM and CMP 48/80 groups had significantly slower rejections and died at day 17.40 ± 1.67 or 14.20 ± 2.28, respectively (P < .05). Rats in the syngeneic group survived more than 60 days. Rejection activity indexes (RAIs) and liver functions were all alleviated through CRM or CMP 48/80 preconditioning. Interferon-γ messenger RNA (mRNA) expressions were reduced and interleukin-10 mRNA levels were higher in allografts in the CRM and CMP 48/80 groups, compared with the PBS group. These were confirmed by testing serum interferon-γ and interlerkin-10.
  
  
  CONCLUSIONS
  Preconditioning donor livers with CRM or CMP 48/80 can reduce AR and prolong survival of recipients after OLT.
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Rao
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; Department of General Surgery, Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: leejiyu@sina.com.
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D004205:Cromolyn Sodium / Q000008:administration & dosage*; D017931:DNA Primers; D016031:Liver Transplantation; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage*
chemical_list: D017931:DNA Primers; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium