PMID- 21256957
OWN - NLM
STAT- MEDLINE
DCOM- 20110808
LR  - 20131121
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 50
IP  - 9
DP  - 2011 May 1
TI  - Maintenance of immune hyporesponsiveness to melanosomal proteins by 
      DHICA-mediated antioxidation: Possible implications for autoimmune vitiligo.
PG  - 1177-85
LID - 10.1016/j.freeradbiomed.2011.01.017 [doi]
AB  - Melanocyte destruction in the skin of vitiligo patients has been considered to be 
      a consequence of an autoimmune response against melanosomal proteins. However, 
      little is known about the molecular mechanisms by which the immune system 
      recognizes these sequestered intracellular self-proteins, which are confined in 
      specialized organelles termed melanosomes, and is provoked into an autoimmune 
      response to melanocytes. Here, we utilize a sucrose density-gradient 
      ultracentrifugation protocol to enrich melanosomal components from dopachrome 
      tautomerase (Dct)-mutant or wild-type melanocytes exposed to a pulse of hydrogen 
      peroxide at a noncytotoxic concentration to evaluate their immunogenicity in mice 
      challenged with the corresponding melanosomal proteins. The results demonstrate 
      that enhanced humoral and cellular immune responses to a challenge with 
      late-stage melanosomal proteins, especially with those derived from Dct-mutant 
      melanocytes, are found in the immunized mice. To elucidate whether a reduced 
      5,6-dihydroxyindole-2-carboxylic acid (DHICA) content in melanin might cause a 
      loss in antioxidative protection to the proteins, we incubated these melanosomal 
      proteins in vitro with synthetic 5,6-dihydroindole (DHI)-melanin or DHI/DHICA 
      (1:1)-melanin and then used them to immunize mice. T cell proliferation and IgG 
      antibody responsiveness to the challenges were significantly induced by 
      melanosomal proteins treated with DHI-melanin, but not by those treated with 
      DHI/DHICA (1:1)-melanin. Moreover, we observed that melanosomal proteins derived 
      from Dct-mutant melanocytes are subject to oxidative modifications that alter 
      their antigenic configurations to attain an enhanced immunogenicity compared with 
      those derived from wild-type melanocytes. From these results, we conclude that 
      DHICA-mediated antioxidation plays a critical role in the maintenance of immune 
      hyporesponsiveness to melanosomal proteins.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Liu, Xiao-Ming
AU  - Liu XM
AD  - Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Zhou, Qiong
AU  - Zhou Q
FAU - Xu, Shi-Zheng
AU  - Xu SZ
FAU - Wakamatsu, Kazumasa
AU  - Wakamatsu K
FAU - Lei, Tie-Chi
AU  - Lei TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110121
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antioxidants)
RN  - 0 (Indoles)
RN  - 0 (Melanins)
RN  - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
MH  - Animals
MH  - Antibody Formation/immunology
MH  - Antioxidants/metabolism
MH  - Autoimmunity
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - *Immune Tolerance
MH  - Immunization, Secondary
MH  - Indoles/chemistry/*metabolism
MH  - Intramolecular Oxidoreductases/genetics/*immunology/metabolism
MH  - *Melanins/immunology/metabolism
MH  - Melanocytes/immunology/metabolism
MH  - Melanosomes/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mutation/genetics/immunology
MH  - Oxidation-Reduction
MH  - Skin/immunology/metabolism/pathology
MH  - T-Lymphocytes/immunology
MH  - Vitiligo/*immunology/metabolism/pathology
EDAT- 2011/01/25 06:00
MHDA- 2011/08/09 06:00
CRDT- 2011/01/25 06:00
PHST- 2010/11/11 00:00 [received]
PHST- 2010/12/21 00:00 [revised]
PHST- 2011/01/12 00:00 [accepted]
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/08/09 06:00 [medline]
AID - S0891-5849(11)00037-2 [pii]
AID - 10.1016/j.freeradbiomed.2011.01.017 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2011 May 1;50(9):1177-85. doi: 
      10.1016/j.freeradbiomed.2011.01.017. Epub 2011 Jan 21.