Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium

Abstract

Background-Phosphatidylserine-expressing microparticles circulate in blood with a short half-life of Ͻ10 minutes. We tested the role of an endothelium-derived phosphatidylserine-binding opsonin, developmental endothelial locus-1 (Del-1), in the uptake of platelet microparticles. Methods and Results-Cultured human umbilical vein and microvascular endothelial cells avidly engulf BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-maleimide-labeled platelet microparticles. Microparticle uptake was inhibited by a monoclonal antibody to Del-1 (Pϭ0.027) and by annexin A5 (Pϭ0.027), abciximab (Pϭ0.027), a monoclonal antibody to integrin ␣V␤3 (Pϭ0.027), and chlorpromazine (Pϭ0.027). These results suggest that Del-1 mediates phosphatidylserine-and integrin-dependent endothelial uptake of microparticles by endocytosis. To assess the in vivo significance, we infused fluorescent platelet microparticles into the inferior vena cava of mice and harvested endothelial cells from the pulmonary and systemic circulation. Compared with their wild-type littermates, Del-1-deficient mice had decreased uptake in endothelial cells in lung (3.07Ϯ1.9 versus 1.09Ϯ1.

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A 2 -IIA

“…A key event in the occurrence of such transfer is the binding of platelet MPs to cells. This may implicate selectins (12) and the recognition of phosphatidylserine, a phospholipid frequently exposed on MPs (13), by lactadherin (14) and developmental endothelial locus-1 (15). Indeed, miRNA-containing platelet MPs are internalized by endothelial cells, thereby altering the stability of mRNA in the recipient (16).…”

Intramicroparticle nitrogen dioxide is a bubble nucleation site leading to decompression-induced neutrophil activation and vascular injury

“…This would likely limit systemic vascular inflammatory responses. Recently, however, an alternative pathway involving MPs binding by Del-1 on endothelial cells opens the way for a systemwide trafficking of MPs that, if delivering a potential toxin such as˙NO 2 , could participate in tissue injury (5).…”

Nouvelle Cuisine: Platelets Served with Inflammation

“…Because they express surface receptors and PS (although some are PS 2 ), microparticles interact with other cells through integrin and via the PS-binding proteins lactaderhin (131) and developmental endothelial locus-1 (Del-1) (132). Hence, lactaderhin 2/2 and Del-1 2/2 mice express higher levels of plasma microparticles compared with their wild-type counterparts, suggesting that these proteins are involved in microparticle clearance and in microparticle interaction with other cells (131,132). Transcription factors packaged inside PMPs can enable transcellular effects, such as PPARg, which was shown to be transported into PMPs and transferred to monocytes where it elicited transcellular effects (129).…”