Phosphatidylserine as an anchor for plasminogen and its plasminogen receptor, Histone H2B, to the macrophage surface

Background: Plasminogen (Plg) binding to cell surface Plg receptors (Plg‐Rs) on the surface of macrophages facilitates Plg activation and migration of these cells. Histone H2B (H2B) acts as a Plg‐R and its cell surface expression is up‐regulated when monocytes are differentiated to macrophages via a...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2011-02, Vol.9 (2), p.339-349
Main Authors: DAS, R., PLOW, E. F.
Format: Article
Language:English
Subjects:
Annexin V
Blotting, Western
Flow Cytometry
histone H2B
Histones - metabolism
Humans
Macrophages - metabolism
phosphatidylserine
Phosphatidylserines - metabolism
plasminogen
Plasminogen - metabolism
plasminogen receptor
Protein Binding
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Summary:Background: Plasminogen (Plg) binding to cell surface Plg receptors (Plg‐Rs) on the surface of macrophages facilitates Plg activation and migration of these cells. Histone H2B (H2B) acts as a Plg‐R and its cell surface expression is up‐regulated when monocytes are differentiated to macrophages via a pathway dependent on L‐type Ca2+ channels and intracellular Ca2+. Objectives: We sought to investigate the mechanism by which H2B, a protein without a transmembrane domain, is retained on the macrophage surface. Methods: THP‐1 monocytoid cells were induced to differentiate with interferon gamma + Vitamin D3 or to undergo apoptosis by treatment with camptothecin. Flow cytometry and cell surface biotinylation followed by Western blotting were used to measure the interrelationship between Plg binding, cell surface expression of H2B and outer membrane exposure of phosphatidylserine (PS). Results: H2B interacted directly with PS via an electrostatic interaction. Anti‐PS or PS binding proteins, annexin V and protein S, diminished H2B interaction with PS on the surface of differentiated or apoptotic cells and these same reagents inhibited Plg binding to these cells. L‐type Ca2+ channels played a significant role in PS exposure, H2B surface expression and Plg binding induced either by differentiation or apoptosis. Conclusions: These data suggest that H2B tethers to the surface of cells by interacting with PS on differentiated or apoptotic monocytoid cells. L‐type Ca2+ channels regulate PS exposure on the surface of these cells. The exposed PS interacts directly with H2B and hence provides sites for Plg to bind to.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2010.04132.x