LSP1

Abstract

Endothelial cells use an actin-binding protein to retract and allow neutrophils to crawl out of blood vessels, according to a new study by Liu et al. (page 409). Figure LSP1 (red) expression in mouse endothelial cells is required for neutrophil transmigration. Neutrophils must traverse the endothelial cell barrier to migrate out of blood vessels into inflamed or injured tissue. Transendothelial migration, once thought to be controlled primarily by the neutrophil, is now known to be a two-way street that requires active participation by both cell types. Endothelial cells respond to neutrophil adhesion by increasing their intracellular calcium levels and rearranging proteins that maintain the tight junctions between neighboring cells. The rearrangement of junctional proteins in endothelial cells ultimately causes them to retract from one another and allows the neutrophils to pass, although the signaling pathways involved are not completely understood.Leukocyte-specific protein 1 (LSP1) is an intracellular actin-binding protein that is expressed in many white blood cells, including neutrophils. LSP1 is a downstream target of kinases that are essential for neutrophil motility and chemotaxis, but the function of LSP1 in neutrophil transmigration remains unclear, as studies using LSP1-deficient mice have produced conflicting results. Liu et al. now show that LSP1 expression is required for neutrophils to traverse the vascular endothelial cell barrier in muscle, as fewer cells were able to cross the endothelium in LSP1-deficient mice. Surprisingly, however, the neutrophils themselves did not need LSP1. Neutrophils lacking LSP1 migrated across wild-type endothelium with the ease of wild-type neutrophils. Wild-type neutrophils, by contrast, could not squeeze through LSP1-deficient endothelial cells. LSP1-deficient mice are resistant to histamine-induced blood vessel leakage which is caused by endothelial cell retraction, suggesting that LSP1 is an indispensable component of the retraction machinery. Exactly how LSP1 links cell surface signals to the cytoskeletal changes that allow retraction remains to be determined.