CO 068: THE LONG PENTRAXIN PTX3: A NON-REDUNDANT COMPONENT OF THE HUMORAL INNATE IMMUNITY AND A PROMISING BIOMARKER IN INFLAMMATORY CONDITIONS

J Pharm Pharmacogn Res 2(Suppl. 1): S42, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 068: THE LONG PENTRAXIN PTX3: A NON-REDUNDANT COMPONENT OF THE HUMORAL INNATE IMMUNITY AND A PROMISING BIOMARKER IN INFLAMMATORY CONDITIONS

Garlanda C, Jaillon S, Barbati E, Bottazzi B, Mantovani A.

Humanitas Clinical and Research Center, via Manzoni 113, Rozzano, 20089, Italy. E-mail: cecilia.garlanda@humanitasresearch.it
Department of Translational Medicine, University of Milan, Milan, Italy.
Abstract

Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver in response to IL-6, while PTX3 is produced by a variety of tissues and cells and in particular by innate immunity cells in response to pro-inflammatory signals and Toll-like receptor (TLR) engagement.

Through in vitro and in vivo studies performed with original tools generated by this group (recombinant human and mouse PTX3, its domains and mutated variants, original anti-PTX3 antibodies and PTX3 gene targeted mice), it has been shown that PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and pathogen recognition by phagocytes, in tuning inflammation and in tissue remodelling. In addition, data obtained so far with ELISA assays on human plasma or serum suggest that PTX3 may represent a useful marker of different inflammatory conditions including cardiovascular pathology complementary to CRP: being directly produced by damaged tissues, its increase precedes CRP and rapidly reflects the vascular involvement by inflammatory process. The combination of PTX3 and classical biomarkers showed an incremental diagnostic and prognostic value in several conditions, including sepsis, acute coronary syndromes and chronic heart failure.

Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor acting as a non-redundant component of the humoral arm of innate immunity and a novel promising biomarker to provide useful prognostic information for clinical outcomes in inflammatory conditions.