The Long Pentraxin 3 Contributes to Joint Inflammation in Gout by Facilitating the Phagocytosis of Monosodium Urate Crystals.

The purpose of this study was to investigate the role of pentraxin 3 (PTX3), a pivotal component of the innate immune system, in gout. Levels of PTX3 and IL-1ß in human samples were evaluated by ELISA. Development of murine gout was evaluated through the levels of cytokines (PTX3, CXCL1, and IL-1ß) and neutrophil recruitment into the joint cavity. Phagocytosis of monosodium urate (MSU) crystals and caspase-1 activation were determined by flow cytometer. Acute gout patients showed elevated concentration of PTX3 in plasma and synovial fluid as compared with healthy and osteoarthritic subjects. Moreover, there was a positive correlation between intra-articular PTX3 and IL-1ß levels. PTX3 was induced in the periarticular tissue of mice postinjection of MSU crystals. Importantly, Ptx3-deficient mice showed reduced inflammation in response to MSU crystal injection compared with wild-type mice, including reduction of neutrophil recruitment into the joint cavity and IL-1ß and CXCL1 production. Interestingly, addition of PTX3 in vitro enhanced MSU crystal phagocytosis by monocytes and resulted in higher production of IL-1ß by macrophages. This contribution of PTX3 to the phagocytosis of MSU crystals and consequent production of IL-1ß occurred through a mechanism mainly dependent on FcγRIII. Thus, our results suggest that PTX3 acts as a humoral pattern recognition molecule in gout facilitating MSU crystal phagocytosis and contributing to the pathogenesis of gouty arthritis.

Pentraxin 3 sputum levels differ in patients with chronic obstructive pulmonary disease vs asthma.

BACKGROUND: Immune response has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma. Pentraxin 3 (PTX3) is a multifunctional pattern recognition protein and an important component of the innate immune system that can be assessed in blood and induced sputum. OBJECTIVE: To determine whether PTX3 measured in induced sputum could discriminate patients with COPD from patients with asthma. METHODS: A cross-sectional study of 68 participants (27 with COPD, 25 with asthma, and 16 healthy controls) was performed. At study inclusion sputum was collected and total and differential cell numbers and PTX3 levels were determined. RESULTS: Pentraxin 3 was detected in 89% of patients with COPD, 56% of patients with asthma, and 19% of controls (P = .001). It discriminated participants with COPD (24.6 ng/mL, 0-384 ng/mL) from controls (0 ng/mL, 0-36 ng/mL, P < .001) and from participants with asthma (1.2 ng/mL, 0-100 ng/mL, P = .01; area under the receiver operating curve 0.82 [0.71-0.94]). Regression analyses determined that sputum PTX3 and neutrophil counts were independently associated with COPD. In addition, PTX3 levels were independently associated with COPD severity. CONCLUSION: Pentraxin 3 sputum levels are increased in patients with COPD and has good power to discriminate these patients from patients with asthma and healthy individuals.