Dangerous connections: neutrophils and the phagocytic clearance of activated platelets.
OBJECTIVE
Platelets and neutrophils co-localize at sites of vessel injury, hemorrhage and thrombosis. Moreover, circulating platelets and leukocytes interact productively, and the formation of heterotypic aggregates is a feature of acute coronary syndromes, systemic inflammatory, neoplastic and autoimmune diseases. We have summarized the evidence suggesting a homeostatic function of the interaction, culminating in the removal of activated platelets from the bloodstream.


RESULTS
Anionic phospholipids, that is cell surface 'eat me' signals exposed both by activated platelets and dying cells, signals such as P-selectin (CD62P), specifically expressed by platelets, as well as of polarized clusters of neutrophils beta2 integrins play a role in the capture of platelets in vitro and in vivo.


CONCLUSIONS
A bona-fide synapse assembles as a consequence of the interaction between P-selectin and its counter-receptor on neutrophils, with clustering of activated beta2 integrins into membrane microdomains and reorganization of cytoskeleton components that control cell motility and phagocytosis. Actual engulfment of the tethered platelet depends on the recognition of phosphatidylserine and/or of phosphatidylserine-associated molecules. This event may have a physiologic role in the regulation of the hemostatic potential of circulating blood; conversely, a failure may contribute to persistent vascular inflammation and thrombosis.
Manfredi
Angelo A
AA
San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy. manfredi.angelo@hsr.it
Rovere-Querini
Patrizia
P
Maugeri
Norma
N
D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology; D010587:Phagocytosis
D019007:P-Selectin