The yin-yang of long pentraxin PTX3 in inflammation and immunity

Abstract

Pentraxins are a family of multimeric proteins characterized by the presence of a pentraxin signature in their C-terminus region. Based on the primary structure, pentraxins are divided into short and long pentraxin: C-reactive protein (CRP) is the prototype of the short pentraxin subfamily while pentraxin 3 (PTX3) is the prototypic long pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.

Keywords: Inflammation; Innate immunity; PTX3; Pentraxin.

Fig. 1

The molecular structures of pentraxin family. (A) Primary structures of human short and long pentraxins. (B) Crystal structures of short pentraxins. Upper panel indicates the pentameric structure of human CRP (Protein Data Bank code 1GNH). The lower panel indicates the structure of human SAP bound to Bis-1,2-{[(Z)-2carboxy-2-methyl-1,3-dioxane]-5-yloxycarbonyl}-piperazine (Protein Data Bank code 2A3X). In SAP two pentamers are interacting face to face to form a decameric structure. (C) Small angle X-ray scattering (SAXS) analysis of PTX3 and its schematic representation. PTX3 N-terminal domain is shown in yellow and C-terminal domain is shown in red, respectively. Panel C is adapted form Inforzato et al. .

Fig. 2

The “yin-yang” effects of PTX3 in infectious or sterile inflammatory conditions. The protective effects of PTX3 are shown in black text and the detrimental effects of PTX3 are shown in white text. The upper half of the panel assigns infectious conditions and the lower half assigns sterile inflammatory conditions.