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Abstract
Autoimmunity is associated with defective phagocytic clearance of apoptotic cells. IgM deficient mice exhibit an autoimmune phenotype consistent with a role for circulating IgM antibodies in apoptotic cell clearance. We have extensively characterised IgM binding to non-apoptotic and apoptotic mouse thymocytes and human Jurkat cells using flow cytometry, confocal imaging and electron microscopy. We demonstrate strong specific IgM binding to a subset of Annexin-V (AnnV)+PI (Propidium Iodide)+ apoptotic cells with disrupted cell membranes. Electron microscopy studies indicated that IgM+AnnV+PI+ apoptotic cells exhibited morphologically advanced apoptosis with marked plasma membrane disruption compared to IgM-AnnV+PI+ apoptotic cells, suggesting that access to intracellular epitopes is required for IgM to bind. Strong and comparable binding of IgM to permeabilised non-apoptotic and apoptotic cells suggests that IgM bound epitopes are 'apoptosis independent' such that IgM may bind any cell with profound disruption of cell plasma membrane integrity. In addition, permeabilised erythrocytes exhibited significant IgM binding thus supporting the importance of cell membrane epitopes. These data suggest that IgM may recognize and tag damaged nucleated cells or erythrocytes that exhibit significant cell membrane disruption. The role of IgM in vivo in conditions characterized by severe cell damage such as ischemic injury, sepsis and thrombotic microangiopathies merits further exploration.
Original language | English |
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Pages (from-to) | e0131849 |
Journal | PLoS ONE |
Volume | 10 |
Issue number | 6 |
DOIs | |
Publication status | Published - 29 Jun 2015 |
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Dive into the research topics of 'Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes'. Together they form a unique fingerprint.Projects
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IgM antibodies exhibit preferential binding to apoptotic and non-apoptotic nucleated cells
Hesketh, E. E. (Creator), Edinburgh DataShare, 5 Mar 2015
DOI: 10.7488/ds/220
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Jeremy Hughes
- Deanery of Clinical Sciences - Personal Chair of Experimental Nephrology
- Centre for Inflammation Research
Person: Academic: Research Active