Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium.
OBJECTIVE
Platelet activation mediates multiple cellular responses, including secretion of chemokines such as RANTES (CCL5), and formation of platelet microparticles (PMPs). We studied the role of PMPs in delivering RANTES and promoting monocyte recruitment.


RESULTS
Here we show that PMPs contain substantial amounts of RANTES and deposit RANTES on activated endothelium or murine atherosclerotic carotid arteries. RANTES deposition is facilitated by flow conditions and more efficient than that conferred by PMP supernatants. Interactions of PMPs with activated endothelium in flow were mostly characterized by rolling. RANTES deposition showed a diffuse distribution pattern and was rarely colocalized with firmly adherent PMPs, substantiating that RANTES deposition occurs during transient interactions. Importantly, preperfusion with PMPs enhanced monocyte arrest on activated endothelium or atherosclerotic carotid arteries, which could be inhibited by a blocking antibody or a RANTES receptor antagonist. Blockade or deficiency of PMP-expressed adhesion receptors demonstrated differential requirement of P-selectin, glycoprotein Ib (GPIb), GPIIb/IIIa, and junctional adhesion molecule-A for PMP interactions with endothelium, PMP-dependent RANTES deposition, and subsequent monocyte arrest.


CONCLUSIONS
Circulating PMPs may serve as a finely tuned transcellular delivery system for RANTES, triggering monocyte arrest to inflamed and atherosclerotic endothelium, introducing a novel mechanism for platelet-dependent monocyte recruitment in inflammation and atherosclerosis.
Mause
Sebastian F
SF
Department of Molecular Cardiovascular Research, University Hospital, Aachen, Germany.
von Hundelshausen
Philipp
P
Zernecke
Alma
A
Koenen
Rory R
RR
Weber
Christian
C
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology* / Q000276:immunology*; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D018946:Chemokine CCL5 / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010316:Particle Size; D015539:Platelet Activation / Q000276:immunology; D013927:Thrombosis / Q000276:immunology*
D001057:Apolipoproteins E; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC