Pentraxins are a superfamily of conserved proteins involved in the acute-phase response and innate immunity. Pentraxin 3 (PTX3), a prototypical member of the long pentraxin subfamily, is a key component of the humoral arm of innate immunity that is essential for resistance to certain pathogens. A regulatory role for pentraxins in inflammation has long been recognized, but the underlying mechanisms remain unclear. Here we report that PTX3 bound P-selectin and attenuated neutrophil recruitment at sites of inflammation. PTX3 released from activated leukocytes functioned locally to dampen neutrophil recruitment and regulate inflammation. Antibodies have glycosylation-dependent regulatory effect on inflammation. Therefore, PTX3, which is an essential component of humoral innate immunity, and immunoglobulins share functional outputs, including complement activation, opsonization and, as shown here, glycosylation-dependent regulation of inflammation.

Doni et al. use four tissue damage models in mice and find that the fluid phase pattern recognition molecule pentraxin 3 (PTX3) plays a role in tissue remodeling and repair. PTX3 binds fibrinogen/fibrin and plasminogen at an acidic pH within tissues. Mice deficient in PTX3 present defects in fibrin deposition, clot formation, collagen deposition, and macrophage-mediated fibrinolysis.

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BackgroundThe renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases.MethodsMale Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured.ResultsIn the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05).ConclusionsAngiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS.