The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dentritic cells

Patrizia Rovere, Giuseppe Peri, Fausto Fazzini, Barbara Bottazzi, Andrea Doni, Attilio Bondanza, Valérie S. Zimmermann, Cecilia Garlanda, Umberto Fascio, Maria Grazia Sabbadini, Claudio Rugarli, Alberto Mantovani, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1β, and tumor necrosis factor-α, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 crosslinking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues.

Original languageEnglish
Pages (from-to)4300-4306
Number of pages7
JournalBlood
Volume96
Issue number13
Publication statusPublished - 2000

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Antigen-Presenting Cells
Cell death
Serum Amyloid P-Component
Cells
Tissue
Acute-Phase Proteins
Interleukin-1
Liver
Crosslinking
C-Reactive Protein
Dendritic Cells
Lipopolysaccharides
Interleukin-6
Cell Death
Tumor Necrosis Factor-alpha
Irradiation
Membranes
Substrates

ASJC Scopus subject areas

  • Hematology

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The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dentritic cells. / Rovere, Patrizia; Peri, Giuseppe; Fazzini, Fausto; Bottazzi, Barbara; Doni, Andrea; Bondanza, Attilio; Zimmermann, Valérie S.; Garlanda, Cecilia; Fascio, Umberto; Sabbadini, Maria Grazia; Rugarli, Claudio; Mantovani, Alberto; Manfredi, Angelo A.

In: Blood, Vol. 96, No. 13, 2000, p. 4300-4306.

Research output: Contribution to journalArticle

Rovere, P, Peri, G, Fazzini, F, Bottazzi, B, Doni, A, Bondanza, A, Zimmermann, VS, Garlanda, C, Fascio, U, Sabbadini, MG, Rugarli, C, Mantovani, A & Manfredi, AA 2000, 'The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dentritic cells', Blood, vol. 96, no. 13, pp. 4300-4306.
Rovere, Patrizia ; Peri, Giuseppe ; Fazzini, Fausto ; Bottazzi, Barbara ; Doni, Andrea ; Bondanza, Attilio ; Zimmermann, Valérie S. ; Garlanda, Cecilia ; Fascio, Umberto ; Sabbadini, Maria Grazia ; Rugarli, Claudio ; Mantovani, Alberto ; Manfredi, Angelo A. / The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dentritic cells. In: Blood. 2000 ; Vol. 96, No. 13. pp. 4300-4306.
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AU - Doni, Andrea

AU - Bondanza, Attilio

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