Stabilin-2 acts as an engulfment receptor for the phosphatidylserine-dependent clearance of primary necrotic cells

Phosphatidylserine (PS) exposed by necrotic cells serves as an engulfment signal for their effective clearance. However, the molecular mechanism responsible for the PS-dependent clearance of necrotic cells remains to be investigated. Here, we show that stabilin-2 acts as a receptor for necrotic cell clearance. Stabilin-2-mediated necrotic cell engulfment occurred in a PS-dependent manner. EGF-like domain repeat (a PS-recognition domain of stabilin-2) bound to necrotic cells and inhibited the stabilin-2-mediated engulfment. However, primary necrotic cells did not induce the anti-inflammatory effect in stabilin-2-expressing cells. These findings facilitate the elucidation of the molecular mechanisms responsible for the PS-dependent clearance of necrotic cells.

► Stabilin-2-expressing cells engulfed heat-killed primary necrotic cells. ► Stabilin-2-mediated engulfment of necrotic cells was phosphatidylserine-dependent. ► EGF-like domain repeat in stabilin-2 directly bound to necrotic cells. ► Necrotic cell recognition by stabilin-2 did not induce anti-inflammatory effect.