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Antibody-mediated platelet phagocytosis by human macrophages is inhibited by siRNA specific for sequences in the SH2 tyrosine kinase, Syk.
- Source :
-
Cellular immunology [Cell Immunol] 2011; Vol. 268 (1), pp. 1-3. Date of Electronic Publication: 2011 Feb 19. - Publication Year :
- 2011
-
Abstract
- Immune thrombocytopenia depends upon Fc receptor-mediated phagocytosis that involves signaling through the SH2 tyrosine kinase, Syk. We designed small interfering (siRNA) sequences complementary to Syk coding regions to decrease the expression of Syk in the human macrophage cell line, THP-1. To evaluate the functional effect of siRNA on phagocytosis, we developed a new in vitro assay for antibody-mediated platelet ingestion by THP-1 cells. Incubation of THP-1 cells at 37°C with fluorescence-labeled platelets and anti-platelet antibody promoted ingestion of platelets that could be quantitated by flow cytometry. Transfection of THP-1 cells with Syk-specific siRNA resulted in a reduction in the amount of FcγRII-associated Syk protein. Coincident with decreased Syk expression, we observed inhibition of antibody-mediated platelet ingestion. These results confirm a key role for Syk in antibody-mediated phagocytosis and suggest Syk-specific siRNA as a possible therapeutic candidate for immune thrombocytopenia.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Biological Assay methods
Cell Line
Down-Regulation
Humans
Intracellular Signaling Peptides and Proteins genetics
Protein-Tyrosine Kinases genetics
Purpura, Thrombocytopenic, Idiopathic physiopathology
Syk Kinase
Antibodies immunology
Blood Platelets cytology
Blood Platelets immunology
Intracellular Signaling Peptides and Proteins metabolism
Macrophages immunology
Phagocytosis drug effects
Protein-Tyrosine Kinases metabolism
RNA, Small Interfering pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2163
- Volume :
- 268
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21382613
- Full Text :
- https://doi.org/10.1016/j.cellimm.2011.02.001