Neutrophils exit veins through protein-sparse regions in the basement membrane (circled).

To migrate out of blood vessels into inflamed tissues, blood cells must cross both the vessel endothelium and basement membrane (BM). According to Wang and colleagues (page 1519), protein-sparse exit sites in the BM pave the way for this cellular escape.

The signals required for blood cells to adhere to sites of vessel inflammation and to squeeze through endothelial cell (EC) junctions are well defined. But it is unclear how the cells then traverse the tough, underlying network of BM proteins. Migrating cells, such as neutrophils, produce proteases that can cleave BM proteins, which may help the cells drill through the BM.

But Wang and colleagues favor a less destructive model, as drilling holes in the BM could inflict irreversible vessel damage. They now show that steady-state expression of certain (but not all) BM proteins—including laminin 10 and collagen IV—is patchy in small veins, creating discrete areas of low protein expression. Most of these low expression regions were aligned with both EC junctions and gaps between pericytes—structural cells that help synthesize BM proteins. These protein-sparse regions appeared to be the preferred sites for inflammation-induced neutrophil exit.

These data suggest that exiting neutrophils take the path of least resistance, a finding that makes perfect sense to senior author Sussan Nourshargh. “If you have a door, you use it,” says Nourshargh. “You don't blast through the wall.”

How neutrophils find these sites, and whether other cell types use the same exits, is now under investigation.