The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice

Danielle G. Souza, Flavio A. Amaral, Caio T. Fagundes, Fernanda M. Coelho, Rosa M E Arantes, Lirlandia P. Sousa, Martin M. Matzuk, Cecilia Garlanda, Alberto Mantovani, Adriana A. Dias, Mauro M. Teixeira

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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 wild-type mice, there was significant local and remote injury as demonstrated by increases in vascular permeability, neutrophil influx, nuclear factor-κB activation, and production of CXCL1 and tumor necrosis factor-α. 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-κB 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 reper- fusion 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 reperfu- sion syndromes.

Original languageEnglish
Pages (from-to)1309-1318
Number of pages10
JournalAmerican Journal of Pathology
Volume174
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Reperfusion
Ischemia
Inflammation
Wounds and Injuries
Neutrophils
Superior Mesenteric Artery
Capillary Permeability
Intestines
Immune System
Tumor Necrosis Factor-alpha
Cytokines
Phenotype
Serum
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Souza, D. G., Amaral, F. A., Fagundes, C. T., Coelho, F. M., Arantes, R. M. E., Sousa, L. P., ... Teixeira, M. M. (2009). The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice. American Journal of Pathology, 174(4), 1309-1318. https://doi.org/10.2353/ajpath.2009.080240

The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice. / Souza, Danielle G.; Amaral, Flavio A.; Fagundes, Caio T.; Coelho, Fernanda M.; Arantes, Rosa M E; Sousa, Lirlandia P.; Matzuk, Martin M.; Garlanda, Cecilia; Mantovani, Alberto; Dias, Adriana A.; Teixeira, Mauro M.

In: American Journal of Pathology, Vol. 174, No. 4, 04.2009, p. 1309-1318.

Research output: Contribution to journalArticle

Souza, DG, Amaral, FA, Fagundes, CT, Coelho, FM, Arantes, RME, Sousa, LP, Matzuk, MM, Garlanda, C, Mantovani, A, Dias, AA & Teixeira, MM 2009, 'The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice', American Journal of Pathology, vol. 174, no. 4, pp. 1309-1318. https://doi.org/10.2353/ajpath.2009.080240
Souza, Danielle G. ; Amaral, Flavio A. ; Fagundes, Caio T. ; Coelho, Fernanda M. ; Arantes, Rosa M E ; Sousa, Lirlandia P. ; Matzuk, Martin M. ; Garlanda, Cecilia ; Mantovani, Alberto ; Dias, Adriana A. ; Teixeira, Mauro M. / The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice. In: American Journal of Pathology. 2009 ; Vol. 174, No. 4. pp. 1309-1318.
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