Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program.
Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 beta2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation.
Maugeri
Norma
N
H San Raffaele Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. maugeri.norma@hsr.it
Rovere-Querini
Patrizia
P
Evangelista
Virgilio
V
Covino
Cesare
C
Capobianco
Annalisa
A
Bertilaccio
Maria T S
MT
Piccoli
Antonio
A
Totani
Licia
L
Cianflone
Domenico
D
Maseri
Attilio
A
Manfredi
Angelo A
AA
D001792:Blood Platelets / Q000276:immunology*; D018821:CD18 Antigens / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D015550:Cell Degranulation; D006801:Humans; D007113:Immunity, Innate; D008562:Membrane Glycoproteins; D009203:Myocardial Infarction / Q000097:blood; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000276:immunology*; D015539:Platelet Activation / Q000276:immunology
D018821:CD18 Antigens; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010718:Phosphatidylserines