Neutrophils phagocytose activated platelets in vivo: A phosphatidylserine, P-selectin, and β2 integrin-dependent cell clearance program

Norma Maugeri, Patrizia Rovere-Querini, Virgilio Evangelista, Cesare Covino, Annalisa Capobianco, Maria T S Bertilaccio, Antonio Piccoli, Licia Totani, Domenico Cianflone, Attilio Maseri, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

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 β2 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.

Original languageEnglish
Pages (from-to)5254-5265
Number of pages12
JournalBlood
Volume113
Issue number21
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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