Pentraxin-3-mediated complement activation in a swine model of renal ischemia/reperfusion injury.

Abstract

Pentraxins are a family of evolutionarily conserved pattern recognition molecules with pivotal roles in innate immunity and inflammation, such as opsonization of pathogens during bacterial and viral infections. In particular, the long Pentraxin 3 (PTX3) has been shown to regulate several aspects of vascular and tissue inflammation during solid organ transplantation. Our study investigated the role of PTX3 as possible modulator of Complement activation in a swine model of renal ischemia/reperfusion (I/R) injury. We demonstrated that I/R injury induced early PTX3 deposits at peritubular and glomerular capillary levels. Confocal laser scanning microscopy revealed PTX3 deposits co-localizing with CD31+ endothelial cells. In addition, PTX3 was associated with infiltrating macrophages (CD163), dendritic cells (SWC3a) and myofibroblasts (FSP1). In particular, we demonstrated a significant PTX3-mediated activation of classical (C1q-mediated) and lectin (MBL-mediated) pathways of Complement. Interestingly, PTX3 deposits co-localized with activation of the terminal Complement complex (C5b-9) on endothelial cells, indicating that PTX3-mediated Complement activation occurred mainly at the renal vascular level. In conclusion, these data indicate that PTX3 might be a potential therapeutic target to prevent Complement-induced I/R injury.

• Authors: Chiara Divella, Alessandra Stasi, Rossana Franzin, Michele Rossini, Paola Pontrelli, Fabio Sallustio, Giuseppe Stefano Netti, Elena Ranieri, Luca Lacitignola, Francesco Staffieri, Alberto Maria Crovace, Giuseppe Lucarelli, Pasquale Ditonno, Michele Battaglia, Mohamed R Daha, Peter van der Pol, Cees van Kooten, Giuseppe Grandaliano, Loreto Gesualdo, Giovanni Stallone, Giuseppe Castellano
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 8 Pg. 10920-10933 (04 20 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 33875620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serum Amyloid P-Component
• PTX3 protein
• C-Reactive Protein

Topics

• Acute Kidney Injury (immunology, pathology)
• Animals
• Biopsy
• C-Reactive Protein (metabolism)
• Complement Activation
• Disease Models, Animal
• Endothelial Cells (immunology, metabolism)
• Endothelium, Vascular (immunology, pathology)
• Female
• Human Umbilical Vein Endothelial Cells
• Humans
• Kidney (blood supply, immunology, pathology)
• Reperfusion Injury (immunology, pathology)
• Serum Amyloid P-Component (metabolism)
• Sus scrofa