Research Paper Volume 13, Issue 8 pp 10920—10933
Pentraxin-3-mediated complement activation in a swine model of renal ischemia/reperfusion injury
- 1 Renal, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- 2 Department of Interdisciplinary Medicine, University of Bari, Bari, Italy
- 3 Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
- 4 Clinical Pathology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
- 5 Veterinary Surgery Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- 6 Urology, Andrology and Renal Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- 7 Department of Nephrology, University of Leiden, Leiden, The Netherlands
- 8 Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- 9 Nephrology, Dialysis and Transplantation Unit, Advanced Research center on Kidney Aging (A.R.K.A.), Department of Medical and Surgical Science, University of Foggia, Foggia, Italy
Received: May 9, 2020 Accepted: March 26, 2021 Published: April 20, 2021https://doi.org/10.18632/aging.202992
How to Cite
Copyright: © 2021 Divella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
I/R: ischemia/reperfusion; EC: endothelial cells; PTX3: pentraxin 3; FSP-1: fibroblast-specific protein 1; N-cadherin: neuronal cadherin; alpha-SMA: alpha-smooth muscle actin.