HDL, PTX3, and Vascular Protection

T he superfamily of pentraxins consists of evolutionary conserved acute phase proteins characterized by the presence of a multimeric structural motif, the pentraxin domain (reviewed in 1 ). C-reactive protein and serum amyloid P represent the short pentraxin arm of this family and are mainly produced by the liver. The long pentraxins were identified more recently as cytokine-inducible molecules expressed in a variety of tissues, and differ from the short pentraxins by the presence of a long N-terminal domain coupled to the C-terminal pentraxin domain. PTX3 was the first recognized member of this family, identified as an interleukin (IL)-1 or tumor necrosis factor (TNF)-inducible gene in several cell types but not in hepatocytes, which contrasts with the short pentraxin CRP, known to be produced in the liver and primarily induced in response to IL-6. Several cell types have been shown to produce significant amounts of PTX3 on activation, including fibroblasts, adipocytes, chondrocytes, or mononuclear phagocytes. Myeloid dendritic cells appear to produce the highest amounts of PTX3 in response to Toll-like receptor engagement and proinflammatory cytokines. In fact, PTX3 is primarily known for its ability to bind selected pathogens and the complement component C1q, and to activate the classical complement pathway, facilitating pathogen recognition by macrophages and dendritic cells, and leading to the induction of a protective immune response. ecent studies have also elegantly shown that PTX3 is stored in specific neutrophil granules, the neutrophil extracellular traps, is rapidly released in response to microbial challenge and inflammatory signals, and plays a critical role in microbial recognition and phagocytosis. 2 Thus, the available evidence clearly points to a nonredundant role for PTX3 in the recognition of selected pathogens, locally at the site of infection, and a role in the rapid amplification of the innate immune response to resist pathogen dissemination.