Phospholipid scramblase 1 is required for β2-glycoprotein I binding in hypoxia and reoxygenation-induced endothelial inflammation.

Abstract

Multiple pathologic conditions, including hemorrhage, tumor angiogenesis, and ischemia-reperfusion events, will result in hypoxia and subsequent reperfusion. Previous studies have analyzed the lipid changes within whole tissues and indicated that ischemia-reperfusion altered tissue and cellular phospholipids. Using an in vitro cell culture model of hypoxia and reoxygenation, we examined the endothelial lipid changes. We hypothesized that phospholipid scramblase 1, a protein that regulates bilayer asymmetry, is involved in altering the phospholipids of endothelial cells during hypoxia, a component of ischemia, leading to β2-glycoprotein I and IgM binding and subsequent lipid-mediated, inflammatory responses. We have completed the first comprehensive study of steady-state phospholipid scramblase 1 mRNA levels, protein expression, and activity under conditions of hypoxia and reoxygenation. Phospholipid scramblase 1 regulates phosphatidylserine exposure in response to oxygen stress, leading to β2-glycoprotein I and IgM binding and lipid-mediated, inflammatory responses.

• Authors: Emily Archer Slone, Michael R Pope, Sherry D Fleming
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 98 Issue 5 Pg. 791-804 (Nov 2015) ISSN: 1938-3673 [Electronic] United States
• PMID: 26216936 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © Society for Leukocyte Biology.

Chemical References

• Immunoglobulin M
• Phospholipid Transfer Proteins
• Plscr1 protein, mouse
• beta 2-Glycoprotein I

Topics

• Animals
• Cell Hypoxia
• Cell Line
• Endothelium, Vascular (metabolism, pathology)
• Immunoglobulin M (genetics, metabolism)
• Inflammation (genetics, metabolism, pathology)
• Mice
• Phospholipid Transfer Proteins (genetics, metabolism)
• Reperfusion Injury (genetics, metabolism, pathology)
• Vasculitis (genetics, metabolism, pathology)
• beta 2-Glycoprotein I (genetics, metabolism)