The Long Pentraxin PTX3 Is Crucial for Tissue Inflammation after Intestinal Ischemia and Reperfusion in Mice

Abstract

The pentraxin superfamily is a group of evolutionarily conserved proteins that play important roles in the immune system. The long pentraxin PTX3 protein was originally described as able to be induced by pro-inflammatory stimuli in a variety of cell types. In this study, we evaluated the phenotype of Ptx3 ؊/؊ mice subjected to ischemia followed by reperfusion of the superior mesenteric artery. In reperfused wildtype mice, there was significant local and remote injury as demonstrated by increases in vascular permeability, neutrophil influx, nuclear factor-B activation, and production of CXCL1 and tumor necrosis factor-␣. PTX3 levels were elevated in both serum and intestine after reperfusion. In Ptx3 ؊/؊ mice, local and remote tissue injury was inhibited, and there were decreased nuclear factor-B translocation and cytokine production. Intestinal architecture was preserved, and there were decreased neutrophil influx and significant prevention of lethality in Ptx3 ؊/؊ mice as well. PTX3 given intravenously before reperfusion reversed the protection observed in Ptx3 ؊/؊ mice in a dose-dependent manner, and PTX3 administration significantly worsened tissue injury and lethality in wild-type mice. In conclusion, our studies demonstrate a major role for PTX3 in determining acute reperfusion-associated inflammation, tissue injury, and lethality and suggest the soluble form of this molecule is active in this system. Therapeutic blockade of PTX3 action may be useful in the control of the injuries associated with severe ischemia and reperfusion syndromes.

Pentraxin 3 Induces Vascular Endothelial Dysfunction Through a P-selectin/Matrix Metalloproteinase-1 Pathway

“…The area under the receiveroperating characteristic curve (AUC) values and 95% confidence intervals are given for the 3 analyzed variables. 33,34 In agreement, PTX3-overexpressing mice had greater tissue damage and mortality after reperfusion of the ischemic vascular bed. 35 Our finding that PTX3 is harmful for the mesenteric district is fully in agreement with previous reports suggesting that therapeutic blockade of the action of PTX3 may be useful for injuries associated with severe ischemia and reperfusion syndromes in the this area.…”

“…A careful analysis of data revealed that overexpression of the protein is induced by different stimuli. 33,35 So far, there are no available data on blood pressure in this experimental condition, and future studies will need to pursue this goal.…”

“…A careful analysis of data revealed that overexpression of the protein is induced by different stimuli. 33,35 So far, there are no available data on blood pressure in this experimental condition, and future studies will need to pursue this goal.Endothelial dysfunction is a typical marker of several cardiovascular disorders such as arterial hypertension. It is still debated whether endothelial dysfunction participates in hypertension or is evoked by high blood pressure.…”

Adenosine Deaminase Inhibition PreventsClostridium difficileToxin A-Induced Enteritis in Mice

“…We also investigated the participation of the long pentraxin 3 (PTX3) in TxA-induced enteritis based on our previous findings pointing out the pivotal role of this protein in injury following intestinal ischemia and reperfusion (49,50). TxA promoted an increase in Ptx3 gene expression in ileal tissue of mice with TxA-induced enteritis compared to that of PBS-injected mice (Fig.…”

Plasma cytokine response, lipid peroxidation and NF-κB activation in skeletal muscle following maximum progressive swimming

“…NF-κB activation was investigated by Western blotting analysis of nuclear cell extracts obtained from homogenized soleus muscle, as described previously (27). Briefly, tissue was homogenized in 1 mL ice-cold hypotonic lysis buffer (10 mM Tris, pH 7.4, 10 mM NaCl, 3 mM MgCl 2 , 0.002% NaN 3 , 1 mM PMSF, 0.1 mM EGTA, 10 µM aprotinin, 20 µM leupeptin, 0.5 mM DTT, 25 mM NaF) and chilled on ice for 15 min and 5% NP-40 was then added for a further 5 min.…”