PMID- 25340603
OWN - NLM
STAT- MEDLINE
DCOM- 20150603
LR  - 20150402
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 99
IP  - 4
DP  - 2015 Apr
TI  - Removal of donor human leukocyte antigen class I proteins with papain: 
      translation for possible whole organ practices.
PG  - 724-30
LID - 10.1097/TP.0000000000000436 [doi]
AB  - BACKGROUND: Papain is a protease with potential use in transplantation because of 
      its targeted capacity to selectively remove human leukocyte antigen (HLA) class I 
      proteins from donor human cells. However, its proteolytic activity has not been 
      studied under conditions suitable for use in perfusing donor organs, namely, 
      under a temperature of 4 degrees C and dissolution in Belzer-UW solution. METHODS: We 
      test papain's HLA class I removing activity under recognized whole organ 
      transplant conditions of lowered temperature. The activity of papain's substrate 
      selectivity was tested using both a test substrate (casein) and fresh peripheral 
      blood lymphocytes (PBLs). The activity of papain was also tested at 4 degrees C, the 
      temperature of whole organ storage. RESULTS: We found that papain at a range of 
      concentrations is nearly as active in cleaving the test substrate in Belzer-UW 
      solution as in distilled water. In distilled water, papain is as active in 
      cleaving a test substrate at a temperature of 4 degrees C as compared to its optimal 
      temperature of 37 degrees C, if the incubation time is extended from 10 min to 3 hr. This 
      finding also holds true if papain is dissolved in Belzer-UW solution. In 
      peripheral blood lymphocytes, papain cleaved off HLA class I proteins as 
      effectively at 4 degrees C as at 37 degrees C, provided the incubation time was also extended to 
      3 hr. CONCLUSION: These findings suggest that papain's targeted enzymatic 
      cleavage of donor HLA class I has potential use in the whole organ transplant 
      setting with retained activity at lower temperatures and when activated and 
      dissolved in Belzer-UW solution.
FAU - Mera, Toshiyuki
AU  - Mera T
AD  - Laboratory of Immunobiology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Faustman, Denise L
AU  - Faustman DL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Caseins)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Insulin)
RN  - 0 (Isoantigens)
RN  - 0 (Organ Preservation Solutions)
RN  - 0 (University of Wisconsin-lactobionate solution)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - EC 3.4.22.2 (Papain)
RN  - GAN16C9B8O (Glutathione)
RN  - K72T3FS567 (Adenosine)
RN  - N5O3QU595M (Raffinose)
SB  - IM
MH  - Adenosine/pharmacology
MH  - Allopurinol/pharmacology
MH  - Caseins/metabolism
MH  - Cold Temperature
MH  - Dose-Response Relationship, Drug
MH  - Glutathione/pharmacology
MH  - HLA Antigens/immunology/*metabolism
MH  - Histocompatibility/*drug effects
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Insulin/pharmacology
MH  - Isoantigens/immunology/*metabolism
MH  - Kinetics
MH  - Lymphocytes/drug effects/enzymology/immunology
MH  - Organ Preservation Solutions/pharmacology
MH  - Organ Transplantation/*adverse effects
MH  - Papain/metabolism/*pharmacology
MH  - Raffinose/pharmacology
MH  - Substrate Specificity
EDAT- 2014/10/24 06:00
MHDA- 2015/06/04 06:00
CRDT- 2014/10/24 06:00
PHST- 2014/10/24 06:00 [entrez]
PHST- 2014/10/24 06:00 [pubmed]
PHST- 2015/06/04 06:00 [medline]
AID - 10.1097/TP.0000000000000436 [doi]
PST - ppublish
SO  - Transplantation. 2015 Apr;99(4):724-30. doi: 10.1097/TP.0000000000000436.