Document Detail


Maintenance of immune hypo-responsiveness to melanosomal proteins by DHICA-mediated antioxidation: Possible implications for autoimmune vitiligo.
MedLine Citation:
PMID:  21256957     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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, to provoke 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 non-cytotoxic concentration to evaluate their immunogenicities 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 the reduced DHICA content in melanin might cause a loss in anti-oxidative protection to the proteins, we incubated these melanosomal proteins in vitro with synthetic 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 hypo-responsiveness to melanosomal proteins.
Authors:
Xiao-Ming Liu; Qiong Zhou; Shi-Zheng Xu; Kazumasa Wakamatsu; Tie-Chi Lei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-20
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
Affiliation:
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
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