The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice.
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-kappaB activation, and production of CXCL1 and tumor necrosis factor-alpha. 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-kappaB 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.
Souza
Danielle G
DG
Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte MG Brazil.
Amaral
Flavio A
FA
Fagundes
Caio T
CT
Coelho
Fernanda M
FM
Arantes
Rosa M E
RM
Sousa
Lirlandia P
LP
Matzuk
Martin M
MM
Garlanda
Cecília
C
Mantovani
Alberto
A
Dias
Adriana A
AA
Teixeira
Mauro M
MM
D000818:Animals; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D016207:Cytokines; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins