Research Paper|Volume 13, Issue 8|pp 10920—10933

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

Chiara Divella¹, Alessandra Stasi¹, Rossana Franzin¹, Michele Rossini¹, Paola Pontrelli¹, Fabio Sallustio^2,³, Giuseppe Stefano Netti⁴, Elena Ranieri⁴, Luca Lacitignola⁵, Francesco Staffieri⁵, Alberto Maria Crovace⁵, Giuseppe Lucarelli⁶, Pasquale Ditonno⁶, Michele Battaglia⁶, Mohamed R. Daha⁷, Peter van der Pol⁷, Cees van Kooten⁷, Giuseppe Grandaliano⁸, Loreto Gesualdo¹, Giovanni Stallone⁹, Giuseppe Castellano⁹

¹Renal, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
²Department of Interdisciplinary Medicine, University of Bari, Bari, Italy
³Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
⁴Clinical Pathology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
⁵Veterinary Surgery Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
⁶Urology, Andrology and Renal Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
⁷Department of Nephrology, University of Leiden, Leiden, The Netherlands
⁸Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
⁹Nephrology, 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, 2020Accepted: March 26, 2021Published: April 20, 2021

https://doi.org/10.18632/aging.202992

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.

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.