Document Detail


Chemical compounds that target thiol-disulfide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells.
MedLine Citation:
PMID:  15752156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Patients having immune cytopenias produce antibodies that target hematopoietic cells resulting in their phagocytosis and intracellular destruction. Early reports suggested that phagocytosis could be inhibited by interfering with membrane thiol (SH) groups on phagocytes. Thus, whether chemical compounds that interact with SH or disulfide (SS) groups on mononuclear phagocytes can inhibit phagocytosis of antibody-coated cells was examined. STUDY DESIGN AND METHODS: A monocyte monolayer assay (MMA), which examines the in vitro monocyte-macrophage (Mphi) interaction with anti-Rh(D)-coated red cells (RBCs), was used to study the ability of different SH and SS chemicals to inhibit the Fc receptor-mediated phagocytosis of sensitized RBCs. The compounds examined included thimerosal, dithiothreitol (DTT), pentane-1-thiol, and two recently described SH and two SS chemicals that have been synthesized. RESULTS: All compounds were found to be able to inhibit phagocytosis to varying degrees correlating to the structure of the molecule. In general, those compounds that interact with free SH groups to inhibit phagocytosis were found better than SH-containing compounds that interact with SSs. Thimerosal and p-nitrophenyl methyl disulfide were the most effective compounds inhibiting phagocytosis. Both chemicals showed greater than 50 percent inhibition at concentrations as low as 10(-9) mol per L. DTT was the least effective compound tested. Only thimerosal showed significant toxicity, as determined by decreased cell viability and increased apoptosis, but only at concentrations of 10(-8) mol per L. The effect of chemical treatment was on attachment rather than on phagocytosis itself. Fcgamma receptor-independent endocytosis was not affected by the chemical treatment. CONCLUSION: These studies indicate that pharmacologic strategies that target SH groups on mononuclear phagocytes may have future efficacy for the treatment of immune cytopenias.
Authors:
Gregory C Rampersad; Garnet Suck; Darinka Sakac; Soad Fahim; Alison Foo; Gregory A Denomme; Richard F Langler; Donald R Branch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transfusion     Volume:  45     ISSN:  0041-1132     ISO Abbreviation:  Transfusion     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-08     Completed Date:  2005-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417360     Medline TA:  Transfusion     Country:  United States    
Other Details:
Languages:  eng     Pagination:  384-93     Citation Subset:  IM    
Affiliation:
Research & Development, Canadian Blood Services, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / immunology
Disulfides / chemistry,  immunology*
Dithiothreitol / pharmacology
Endocytosis / immunology
Erythrocytes / immunology*
Humans
Macrophages / immunology
Monocytes / immunology
Phagocytes / immunology*
Phagocytosis / drug effects,  immunology*
Preservatives, Pharmaceutical / chemistry,  pharmacology
Receptors, IgG / immunology
Rh-Hr Blood-Group System / immunology
Sulfhydryl Compounds / chemistry,  immunology*
Thimerosal / chemistry,  pharmacology
Chemical
Reg. No./Substance:
0/Antibodies; 0/Disulfides; 0/Preservatives, Pharmaceutical; 0/Receptors, IgG; 0/Rh-Hr Blood-Group System; 0/Rho(D) antigen; 0/Sulfhydryl Compounds; 3483-12-3/Dithiothreitol; 54-64-8/Thimerosal

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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