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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4300-4306
IMMUNOBIOLOGY
The long pentraxin PTX3 binds to apoptotic cells and regulates
their clearance by antigen-presenting dendritic 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, and
Angelo A. Manfredi
From the Tumor Immunology Laboratory and Cancer
Immunotherapy and Gene Therapy Program, Istituto Scientifico H S. Raffaele and Vita-Salute San Raffaele University; Department of
Biology, University of Milan and Istituto di Ricerche Farmacologiche
"Mario Negri," Milan, Italy; and the Sezione di Patologia e
Immunologia, Dipartimento di Biotecnologie, Università di
Brescia, Brescia, Italy.
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-1 , and tumor necrosis factor- , 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 cross-linking-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.
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