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

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 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.

The long pentraxin 3 is a soluble and cell‐associated component of the human semen

“…The long pentraxin 3 is implicated in the recognition and clearance of apoptotic cells (Rovere et al, 2000;van Rossum et al, 2004). Apoptosis occurs in the testis and in normal spermatogenesis (Muratori et al, 2006).…”

“…It is produced by innate-immunity cells in response to pro-inflammatory signals and acts as a predecessor of antibodies, regulates complement activation, facilitates pathogen recognition by phagocytes and directly recognizes some selected fungal and bacterial microorganisms such as Aspergillus fumigatus, Pseudomonas aeruginosa and Salmonella typhymurium (Garlanda et al, 2005;Bottazzi et al, 2006). PTX3 also binds apoptotic cells (Rovere et al, 2000) and may contribute to editing recognition of apoptotic cells vs. infectious nonself (Baruah et al, 2006). In addition, there is evidence for a regulatory role of PTX3 in non-infectious inflammatory reactions (Souza et al, 2002;Salio et al, unpublished data).…”

The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis

“…On the contrary, when the interaction between PTX3 and C1q occurs in fluid phase, an impairment of C1q and C3 deposition on apoptotic cells is observed, as well as a reduction in C1q-meditated phagocytosis by DCs and macrophages ( Figure 1). 97,102,103 DCs in particular have a pivotal role in the removal of apoptotic cell debris and their presentation to T cells. PTX3 is stably bound to both the surface of dying cells and DCs: interestingly, the crosspresentation of epitopes deriving from PTX3-apoptotic cells to T cells is reduced, limiting tissue damage and activation of autoreactive T cell under inflammatory conditions.…”

Role of the soluble pattern recognition receptor PTX3 in vascular biology

“…This will affect endothelial cell functions and integrity. [25,47,[53][54][55] C1s no [25] Short-pentraxin ligands phosphorylcoline no [25] phosphoethanolamine no [25] high pyruvate agarose no [25] histones yes [25,44] Isolated microbial components zymosan yes [48] KpOmpA yes [51] ECM components hyaluronic acid no [35] TSG6 yes [35] heparin/HSPGs no * type IV collagen no [25,44] fibronectin no [25,44] vitronectin no [44] Eukariotic cell surfaces/receptors apoptotic cell extranuclear membrane yes [82] A-type K(+) channel yes [105] integrins no * gangliosides no * HSPGs no *…”